Conference Coverage

Among high-risk early breast cancer patients, a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from a phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.

“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.

“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.

The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.

Among high-risk early breast cancer patients, a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from a phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.

“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.

“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.

The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.

Among high-risk early breast cancer patients, a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from a phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.

“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.

“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.

The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.

“The right drug at the right time with the right dose for the right bug for the right duration.” That, said professor Kristina Crothers, MD, is the general guidance for optimizing antibiotic use (while awaiting an infectious disease consult). In her oral presentation at the annual meeting of the American College of Chest Physicians, “Choosing newer antibiotics for nosocomial pneumonia,” Dr. Crothers asked the question: “Beyond the guidelines: When should novel antimicrobials be used?”

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common nosocomial infections at 22%, and are the leading cause of death attributable to hospital-acquired infections. They increase mortality by 20%-50%, with an economic burden of about $40,000 per patient. The incidence of multidrug-resistant (MDR) organism infections varies widely by locality, but several factors increase the likelihood: prior broad-spectrum antibiotic exposure within the past 90 days; longer hospitalization; indwelling vascular devices; tracheostomy; and ventilator dependence. The Centers for Disease Control and Prevention lists as “Serious Threat” the HAP/VAP MDR organisms methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PSA) with difficult-to-treat-resistance, and beta-lactamase producing Enterobacterales (ESBL). In the category of “Urgent Threat” the CDC lists: carbapenamase-resistant Enterobacterales (CRE) (carbapenamase producing or non–carbapenemase producing), and carbapenem-resistant Acinetobacter (CRAB), according to Dr. Crothers who is at the University of Washington Veterans Affairs Puget Sound Health Care System, Seattle.

Newer antibiotics for HAP/VAP that are still beyond the guidelines include telavancin and tedizolid as gram-positive agents, and as gram-negative ones: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, imipenem-cilastatin-relebactam and meropenem-vaborbactam, she added.
 

Tedizolid, Dr. Crothers stated, is a novel oxazolidinone, and is an alternative to vancomycin and linezolid for gram-positive HAP/VAP. In the VITAL noninferiority study versus linezolid with 726 patients, it was noninferior to linezolid for 28-day all-cause mortality (28% vs. 26%), but did not achieve noninferiority for investigator-assessed clinical cure (56% vs. 64%).

Televancin, a semisynthetic derivative of vancomycin, in the ATTAIN studies vs. vancomycin had overall similar cure rates. It is FDA-approved for S. aureus HAP/VAP but not other bacterial causes. It should be reserved for those who cannot receive vancomycin or linezolid, with normal renal function, according to Dr. Crothers. Excluded from first-line treatment of gram-positive HAP/VAP are daptomycin, ceftaroline, ceftobiprole, and tigecycline.

Ceftazidime-avibactam, a third-generation cephalosporin-plus novel beta-lactamase inhibitor has wide activity (Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, PSA and Haemophilus influenzae. It is also active against some extended-spectrum beta-lactamases (ESBLs), ampC beta-lactamases (AmpCs), and K. pneumoniae carbapenemase (KPC)–producing Enterobacterales, but not with metallo-beta-lactamases). Ceftazidime-avibactam is also indicated for HAP/VAP, and has a toxicity profile including nausea, vomiting, and diarrhea.

In the REPROVE trial of ceftazidime-avibactam vs. meropenem for 7-14 days with 527 clinically evaluable patients (37% K. pneumoniae, 30% P. aeruginosa, and 33%-35% VAP), the clinical cure at 21-25 days post randomization was 69% vs. 73%, respectively, with similar adverse events.
 

Ceftolozane-tazobactam, a novel fifth-generation cephalosporin plus a beta-lactamase inhibitor has activity against PSA including extensively drug-resistant PSA, AmpC, and ESBL-E, but it has limited activity against Acinetobacter and Stenotrophomonas. It is indicated for HAP/VAP, has reduced efficacy with creatine clearance of 50 mL/min or less, increases transaminases and renal impairment, and causes diarrhea. In ASPECT-NP (n = 726) ceftolozane-tazobactam versus meropenem for 8-14 days (HAP/VAP), showed a 28 day-mortality of 24% vs. 25%, respectively, with test of cure at 54% vs. 53% at 7-14 days post therapy. Adverse events were similar between groups.

Imipenem-cilastatin-relebactam, a novel beta-lactamase inhibitor plus carbapenem, is indicated for HAP/VAP and has activity against ESBL, CRE: KPC-producing Enterobacterales, PSA including AmpC. It can cause seizures (requires caution with central nervous system disorders and renal impairment). It increases transaminases, anemia, diarrhea, and reduces potassium and sodium. In RESTORE-IMI 2 (n = 537 with HAP/VAP) it was noninferior for 28-day all-cause mortality vs. piperacillin and tazobactam (16% vs. 21%), with similar adverse events.

Cefiderocol, a siderophore cephalosporin, is indicated for HAP/VAP. It has a wide spectrum of activity: ESBL, CRE, CR PSA, Stenotrophomonas maltophilia, Acinetobacter baumanii, Streptococcus.) It increases transaminases, diarrhea, and atrial fibrillation, and it reduces potassium and magnesium. In APEKS-NP versus linezolid plus cefiderocol or extended meropenem infusion (HAP/VAP n = 292; gram-negative pneumonia = 251; 60% invasive mechanical ventilation) it was noninferior for 14-day all-cause mortality (12.4% vs. 11.6%) with similar adverse events. In CREDIBLE-CR vs. best available therapy for carbapenem-resistant gram-negative infections, clinical cure rates were similar (50% vs. 53% in 59 HAP/VAP patients at 7 days), but with more deaths in the cefiderocol arm. Adverse events were > 90% in both groups and 34% vs. 19% died, mostly with Acinetobacter.

Meropenem-vaborbactam, a novel beta-lactamase inhibitor plus carbapenem, is approved and indicated for HAP/VAP in Europe. It has activity against MDR, Enterobacterales including CRE. Its toxicities include headache, phlebitis/infusion-site reactions and diarrhea. In TANGO-2 versus best available treatment for carbapenem-resistant Enterobacteriaceae (CRE) (n = 77, 47 with confirmed CRE), clinical cure was increased and mortality decreased compared with best available therapy. Treatment- and renal-related adverse events were lower for meropenem-vaborbactam.

In closing, Dr. Crothers cited advice from the paper by Tamma et al. (“Rethinking how Antibiotics are Prescribed” JAMA. 2018) about the need to review findings after therapy has been initiated to confirm the pneumonia diagnosis: Novel agents should be kept in reserve in the absence of MDR risk factors for MRSA and gram-negative bacilli; therapy should be deescalated after 48-72 hours if MDR organisms are not detected; and therapy should be directed to the specific organism detected. Most HAP and VAP in adults can be treated for 7 days, she added.

“Know indications for new therapeutic agents approved for nosocomial pneumonia,” she concluded.

Dr. Crothers reported having no disclosures.

“The right drug at the right time with the right dose for the right bug for the right duration.” That, said professor Kristina Crothers, MD, is the general guidance for optimizing antibiotic use (while awaiting an infectious disease consult). In her oral presentation at the annual meeting of the American College of Chest Physicians, “Choosing newer antibiotics for nosocomial pneumonia,” Dr. Crothers asked the question: “Beyond the guidelines: When should novel antimicrobials be used?”

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common nosocomial infections at 22%, and are the leading cause of death attributable to hospital-acquired infections. They increase mortality by 20%-50%, with an economic burden of about $40,000 per patient. The incidence of multidrug-resistant (MDR) organism infections varies widely by locality, but several factors increase the likelihood: prior broad-spectrum antibiotic exposure within the past 90 days; longer hospitalization; indwelling vascular devices; tracheostomy; and ventilator dependence. The Centers for Disease Control and Prevention lists as “Serious Threat” the HAP/VAP MDR organisms methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PSA) with difficult-to-treat-resistance, and beta-lactamase producing Enterobacterales (ESBL). In the category of “Urgent Threat” the CDC lists: carbapenamase-resistant Enterobacterales (CRE) (carbapenamase producing or non–carbapenemase producing), and carbapenem-resistant Acinetobacter (CRAB), according to Dr. Crothers who is at the University of Washington Veterans Affairs Puget Sound Health Care System, Seattle.

Newer antibiotics for HAP/VAP that are still beyond the guidelines include telavancin and tedizolid as gram-positive agents, and as gram-negative ones: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, imipenem-cilastatin-relebactam and meropenem-vaborbactam, she added.
 

Tedizolid, Dr. Crothers stated, is a novel oxazolidinone, and is an alternative to vancomycin and linezolid for gram-positive HAP/VAP. In the VITAL noninferiority study versus linezolid with 726 patients, it was noninferior to linezolid for 28-day all-cause mortality (28% vs. 26%), but did not achieve noninferiority for investigator-assessed clinical cure (56% vs. 64%).

Televancin, a semisynthetic derivative of vancomycin, in the ATTAIN studies vs. vancomycin had overall similar cure rates. It is FDA-approved for S. aureus HAP/VAP but not other bacterial causes. It should be reserved for those who cannot receive vancomycin or linezolid, with normal renal function, according to Dr. Crothers. Excluded from first-line treatment of gram-positive HAP/VAP are daptomycin, ceftaroline, ceftobiprole, and tigecycline.

Ceftazidime-avibactam, a third-generation cephalosporin-plus novel beta-lactamase inhibitor has wide activity (Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, PSA and Haemophilus influenzae. It is also active against some extended-spectrum beta-lactamases (ESBLs), ampC beta-lactamases (AmpCs), and K. pneumoniae carbapenemase (KPC)–producing Enterobacterales, but not with metallo-beta-lactamases). Ceftazidime-avibactam is also indicated for HAP/VAP, and has a toxicity profile including nausea, vomiting, and diarrhea.

In the REPROVE trial of ceftazidime-avibactam vs. meropenem for 7-14 days with 527 clinically evaluable patients (37% K. pneumoniae, 30% P. aeruginosa, and 33%-35% VAP), the clinical cure at 21-25 days post randomization was 69% vs. 73%, respectively, with similar adverse events.
 

Ceftolozane-tazobactam, a novel fifth-generation cephalosporin plus a beta-lactamase inhibitor has activity against PSA including extensively drug-resistant PSA, AmpC, and ESBL-E, but it has limited activity against Acinetobacter and Stenotrophomonas. It is indicated for HAP/VAP, has reduced efficacy with creatine clearance of 50 mL/min or less, increases transaminases and renal impairment, and causes diarrhea. In ASPECT-NP (n = 726) ceftolozane-tazobactam versus meropenem for 8-14 days (HAP/VAP), showed a 28 day-mortality of 24% vs. 25%, respectively, with test of cure at 54% vs. 53% at 7-14 days post therapy. Adverse events were similar between groups.

Imipenem-cilastatin-relebactam, a novel beta-lactamase inhibitor plus carbapenem, is indicated for HAP/VAP and has activity against ESBL, CRE: KPC-producing Enterobacterales, PSA including AmpC. It can cause seizures (requires caution with central nervous system disorders and renal impairment). It increases transaminases, anemia, diarrhea, and reduces potassium and sodium. In RESTORE-IMI 2 (n = 537 with HAP/VAP) it was noninferior for 28-day all-cause mortality vs. piperacillin and tazobactam (16% vs. 21%), with similar adverse events.

Cefiderocol, a siderophore cephalosporin, is indicated for HAP/VAP. It has a wide spectrum of activity: ESBL, CRE, CR PSA, Stenotrophomonas maltophilia, Acinetobacter baumanii, Streptococcus.) It increases transaminases, diarrhea, and atrial fibrillation, and it reduces potassium and magnesium. In APEKS-NP versus linezolid plus cefiderocol or extended meropenem infusion (HAP/VAP n = 292; gram-negative pneumonia = 251; 60% invasive mechanical ventilation) it was noninferior for 14-day all-cause mortality (12.4% vs. 11.6%) with similar adverse events. In CREDIBLE-CR vs. best available therapy for carbapenem-resistant gram-negative infections, clinical cure rates were similar (50% vs. 53% in 59 HAP/VAP patients at 7 days), but with more deaths in the cefiderocol arm. Adverse events were > 90% in both groups and 34% vs. 19% died, mostly with Acinetobacter.

Meropenem-vaborbactam, a novel beta-lactamase inhibitor plus carbapenem, is approved and indicated for HAP/VAP in Europe. It has activity against MDR, Enterobacterales including CRE. Its toxicities include headache, phlebitis/infusion-site reactions and diarrhea. In TANGO-2 versus best available treatment for carbapenem-resistant Enterobacteriaceae (CRE) (n = 77, 47 with confirmed CRE), clinical cure was increased and mortality decreased compared with best available therapy. Treatment- and renal-related adverse events were lower for meropenem-vaborbactam.

In closing, Dr. Crothers cited advice from the paper by Tamma et al. (“Rethinking how Antibiotics are Prescribed” JAMA. 2018) about the need to review findings after therapy has been initiated to confirm the pneumonia diagnosis: Novel agents should be kept in reserve in the absence of MDR risk factors for MRSA and gram-negative bacilli; therapy should be deescalated after 48-72 hours if MDR organisms are not detected; and therapy should be directed to the specific organism detected. Most HAP and VAP in adults can be treated for 7 days, she added.

“Know indications for new therapeutic agents approved for nosocomial pneumonia,” she concluded.

Dr. Crothers reported having no disclosures.

“The right drug at the right time with the right dose for the right bug for the right duration.” That, said professor Kristina Crothers, MD, is the general guidance for optimizing antibiotic use (while awaiting an infectious disease consult). In her oral presentation at the annual meeting of the American College of Chest Physicians, “Choosing newer antibiotics for nosocomial pneumonia,” Dr. Crothers asked the question: “Beyond the guidelines: When should novel antimicrobials be used?”

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common nosocomial infections at 22%, and are the leading cause of death attributable to hospital-acquired infections. They increase mortality by 20%-50%, with an economic burden of about $40,000 per patient. The incidence of multidrug-resistant (MDR) organism infections varies widely by locality, but several factors increase the likelihood: prior broad-spectrum antibiotic exposure within the past 90 days; longer hospitalization; indwelling vascular devices; tracheostomy; and ventilator dependence. The Centers for Disease Control and Prevention lists as “Serious Threat” the HAP/VAP MDR organisms methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PSA) with difficult-to-treat-resistance, and beta-lactamase producing Enterobacterales (ESBL). In the category of “Urgent Threat” the CDC lists: carbapenamase-resistant Enterobacterales (CRE) (carbapenamase producing or non–carbapenemase producing), and carbapenem-resistant Acinetobacter (CRAB), according to Dr. Crothers who is at the University of Washington Veterans Affairs Puget Sound Health Care System, Seattle.

Newer antibiotics for HAP/VAP that are still beyond the guidelines include telavancin and tedizolid as gram-positive agents, and as gram-negative ones: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, imipenem-cilastatin-relebactam and meropenem-vaborbactam, she added.
 

Tedizolid, Dr. Crothers stated, is a novel oxazolidinone, and is an alternative to vancomycin and linezolid for gram-positive HAP/VAP. In the VITAL noninferiority study versus linezolid with 726 patients, it was noninferior to linezolid for 28-day all-cause mortality (28% vs. 26%), but did not achieve noninferiority for investigator-assessed clinical cure (56% vs. 64%).

Televancin, a semisynthetic derivative of vancomycin, in the ATTAIN studies vs. vancomycin had overall similar cure rates. It is FDA-approved for S. aureus HAP/VAP but not other bacterial causes. It should be reserved for those who cannot receive vancomycin or linezolid, with normal renal function, according to Dr. Crothers. Excluded from first-line treatment of gram-positive HAP/VAP are daptomycin, ceftaroline, ceftobiprole, and tigecycline.

Ceftazidime-avibactam, a third-generation cephalosporin-plus novel beta-lactamase inhibitor has wide activity (Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, PSA and Haemophilus influenzae. It is also active against some extended-spectrum beta-lactamases (ESBLs), ampC beta-lactamases (AmpCs), and K. pneumoniae carbapenemase (KPC)–producing Enterobacterales, but not with metallo-beta-lactamases). Ceftazidime-avibactam is also indicated for HAP/VAP, and has a toxicity profile including nausea, vomiting, and diarrhea.

In the REPROVE trial of ceftazidime-avibactam vs. meropenem for 7-14 days with 527 clinically evaluable patients (37% K. pneumoniae, 30% P. aeruginosa, and 33%-35% VAP), the clinical cure at 21-25 days post randomization was 69% vs. 73%, respectively, with similar adverse events.
 

Ceftolozane-tazobactam, a novel fifth-generation cephalosporin plus a beta-lactamase inhibitor has activity against PSA including extensively drug-resistant PSA, AmpC, and ESBL-E, but it has limited activity against Acinetobacter and Stenotrophomonas. It is indicated for HAP/VAP, has reduced efficacy with creatine clearance of 50 mL/min or less, increases transaminases and renal impairment, and causes diarrhea. In ASPECT-NP (n = 726) ceftolozane-tazobactam versus meropenem for 8-14 days (HAP/VAP), showed a 28 day-mortality of 24% vs. 25%, respectively, with test of cure at 54% vs. 53% at 7-14 days post therapy. Adverse events were similar between groups.

Imipenem-cilastatin-relebactam, a novel beta-lactamase inhibitor plus carbapenem, is indicated for HAP/VAP and has activity against ESBL, CRE: KPC-producing Enterobacterales, PSA including AmpC. It can cause seizures (requires caution with central nervous system disorders and renal impairment). It increases transaminases, anemia, diarrhea, and reduces potassium and sodium. In RESTORE-IMI 2 (n = 537 with HAP/VAP) it was noninferior for 28-day all-cause mortality vs. piperacillin and tazobactam (16% vs. 21%), with similar adverse events.

Cefiderocol, a siderophore cephalosporin, is indicated for HAP/VAP. It has a wide spectrum of activity: ESBL, CRE, CR PSA, Stenotrophomonas maltophilia, Acinetobacter baumanii, Streptococcus.) It increases transaminases, diarrhea, and atrial fibrillation, and it reduces potassium and magnesium. In APEKS-NP versus linezolid plus cefiderocol or extended meropenem infusion (HAP/VAP n = 292; gram-negative pneumonia = 251; 60% invasive mechanical ventilation) it was noninferior for 14-day all-cause mortality (12.4% vs. 11.6%) with similar adverse events. In CREDIBLE-CR vs. best available therapy for carbapenem-resistant gram-negative infections, clinical cure rates were similar (50% vs. 53% in 59 HAP/VAP patients at 7 days), but with more deaths in the cefiderocol arm. Adverse events were > 90% in both groups and 34% vs. 19% died, mostly with Acinetobacter.

Meropenem-vaborbactam, a novel beta-lactamase inhibitor plus carbapenem, is approved and indicated for HAP/VAP in Europe. It has activity against MDR, Enterobacterales including CRE. Its toxicities include headache, phlebitis/infusion-site reactions and diarrhea. In TANGO-2 versus best available treatment for carbapenem-resistant Enterobacteriaceae (CRE) (n = 77, 47 with confirmed CRE), clinical cure was increased and mortality decreased compared with best available therapy. Treatment- and renal-related adverse events were lower for meropenem-vaborbactam.

In closing, Dr. Crothers cited advice from the paper by Tamma et al. (“Rethinking how Antibiotics are Prescribed” JAMA. 2018) about the need to review findings after therapy has been initiated to confirm the pneumonia diagnosis: Novel agents should be kept in reserve in the absence of MDR risk factors for MRSA and gram-negative bacilli; therapy should be deescalated after 48-72 hours if MDR organisms are not detected; and therapy should be directed to the specific organism detected. Most HAP and VAP in adults can be treated for 7 days, she added.

“Know indications for new therapeutic agents approved for nosocomial pneumonia,” she concluded.

Dr. Crothers reported having no disclosures.

SAN FRANCISCO – Widely anticipated data from a phase 3 trial of the monoclonal antibody lecanemab suggest the drug “modestly” relieved cognitive impairment in patients with early Alzheimer’s disease (AD) – but at a cost.

In the CLARITY AD trial, adverse events (AEs) were common compared with placebo, including amyloid-related edema and effusions; and a recent news report linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” wrote Christopher H. van Dyck, MD, Yale University, New Haven, Conn., and colleagues.

The full trial findings were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, with simultaneous publication on Nov. 29 in the New England Journal of Medicine.
 

Complications in the field

The phase 3 trial of lecanemab has been closely watched in AD circles, especially considering positive early data released in September and reported by this news organization at that time.

The Food and Drug Administration is expected to make a decision about possible approval of the drug in January 2023. Only one other antiamyloid treatment, the highly controversial and expensive aducanumab (Aduhelm), is currently approved by the FDA.

For the new 18-month, randomized, double-blind CLARITY AD trial, researchers enrolled 1,795 patients aged 50-90 years (average age, 71 years) with early AD. All were randomly assigned to receive either a placebo (n = 898) or intravenous lecanemab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets amyloid beta (A-beta) protofibrils, at 10 mg/kg of body weight every 2 weeks (n = 897).

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. Safety data included all participants, and the modified intention-to-treat group included 1,734 participants, with 859 receiving lecanemab and 875 receiving placebo.

The primary endpoint was the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Scores from 0.5 to 6 are signs of early AD, according to the study. The mean baseline score for both groups was 3.2. The adjusted mean change at 18 months was 1.21 for lecanemab versus 1.66 for placebo (difference, –0.45; 95% confidence interval [CI], –0.67 to –0.23; P < .001).

As Dr. van Dyck noted in his presentation at the CTAD meting, this represents a 27% slowing of the decline in the lecanemab group.

The published findings do not speculate about how this difference would affect the day-to-day life of participants who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Other measurements that suggest cognitive improvements in the lecanemab group versus placebo include the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score (mean difference, –1.44; 95% CI, –2.27 to –0.61), the Alzheimer’s Disease Composite Score (mean difference, –0.05; 95% CI, –.074 to –.027,), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment score (mean difference, 2.0; 95% CI, 1.2-2.8; all, P < .001).

Overall, Dr. van Dyck said, “Lecanemab met the primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months.”

In a substudy of 698 participants, results showed that amyloid burden fell at a higher rate in the lecanemab group than in the placebo group (difference, –59.1 centiloids; 95% CI, –62.6 to –55.6).

“Lecanemab has high selectivity for soluble aggregated species of A-beta as compared with monomeric amyloid, with moderate selectivity for fibrillar amyloid; this profile is considered to target the most toxic pathologic amyloid species,” the researchers wrote.
 

Concerning AE data

With respect to AEs, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, according to a report in the journal Science published Nov. 27, a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Researchers summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

In a CTAD presentation, study coauthor Marwan Sabbagh, MD, Barrow Neurological Institute, Phoenix, said two hemorrhage-related deaths occurred in an open-label extension. One was in the context of a tissue plasminogen activator treatment for a stroke, which fits with the description of the case in the Science report. “Causality with lecanemab is a little difficult ...,” he said. “Patients on anticoagulation might need further consideration.”

In the CLARITY AD Trial, serious AEs occurred in 14% of the lecanemab group, leading to discontinuation 6.9% of the time, and in 11.3% of the placebo group, leading to discontinuation 2.9% of the time, the investigators reported.

They added that, in the lecanemab group, the most common AEs, defined as affecting more than 10% of participants, were infusion-related reactions (26.4% vs. 7.4% for placebo); amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (17.3% vs. 9%, respectively); amyloid-related imaging abnormalities with edema or effusions (12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% vs. 9.6%).

In addition, macrohemorrhage was reported in 0.6% of the lecanemab group and 0.1% of the placebo group.
 

Cautious optimism

In separate interviews, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive, owing to the large investment needed for research, he added, and patients will have to undergo costly testing, such as PET scans and spinal taps.

Still, “this could be a valuable adjunct to the armamentarium we have,” which includes interventions such as lifestyle changes, he said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and that the drug had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially among patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal – fully reversing cognitive decline.

Michael Weiner, MD, president of the CTAD22 Scientific Committee, noted in a press release that there is “growing evidence” that some antiamyloid therapies, “especially lecanemab and donanemab” have shown promising results.

“Unfortunately, these treatments are also associated with abnormal differences seen in imaging, including brain swelling and bleeding in the brain,” said Dr. Weiner, professor of radiology, medicine, and neurology at the University of California, San Francisco.

“There is considerable controversy concerning the significance and impact of these findings, including whether or not governments and medical insurance will provide financial coverage for such treatments,” he added.
 

Rave reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared that the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease ...” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is a staunch supporter of aducanumab, called on the Centers for Medicare & Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the two reported deaths.

The trial was supported by Eisai (regulatory sponsor) with partial funding from Biogen. Dr. van Dyck reports having received research grants from Biogen, Eisai, Biohaven, Cerevel Therapeutics, Eli Lilly, Genentech, Janssen, Novartis, and UCB. He has been a consultant to Cerevel, Eisai, Ono Pharmaceutical, and Roche. Relevant financial relationships for the other investigators are fully listed in the original article.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Widely anticipated data from a phase 3 trial of the monoclonal antibody lecanemab suggest the drug “modestly” relieved cognitive impairment in patients with early Alzheimer’s disease (AD) – but at a cost.

In the CLARITY AD trial, adverse events (AEs) were common compared with placebo, including amyloid-related edema and effusions; and a recent news report linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” wrote Christopher H. van Dyck, MD, Yale University, New Haven, Conn., and colleagues.

The full trial findings were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, with simultaneous publication on Nov. 29 in the New England Journal of Medicine.
 

Complications in the field

The phase 3 trial of lecanemab has been closely watched in AD circles, especially considering positive early data released in September and reported by this news organization at that time.

The Food and Drug Administration is expected to make a decision about possible approval of the drug in January 2023. Only one other antiamyloid treatment, the highly controversial and expensive aducanumab (Aduhelm), is currently approved by the FDA.

For the new 18-month, randomized, double-blind CLARITY AD trial, researchers enrolled 1,795 patients aged 50-90 years (average age, 71 years) with early AD. All were randomly assigned to receive either a placebo (n = 898) or intravenous lecanemab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets amyloid beta (A-beta) protofibrils, at 10 mg/kg of body weight every 2 weeks (n = 897).

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. Safety data included all participants, and the modified intention-to-treat group included 1,734 participants, with 859 receiving lecanemab and 875 receiving placebo.

The primary endpoint was the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Scores from 0.5 to 6 are signs of early AD, according to the study. The mean baseline score for both groups was 3.2. The adjusted mean change at 18 months was 1.21 for lecanemab versus 1.66 for placebo (difference, –0.45; 95% confidence interval [CI], –0.67 to –0.23; P < .001).

As Dr. van Dyck noted in his presentation at the CTAD meting, this represents a 27% slowing of the decline in the lecanemab group.

The published findings do not speculate about how this difference would affect the day-to-day life of participants who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Other measurements that suggest cognitive improvements in the lecanemab group versus placebo include the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score (mean difference, –1.44; 95% CI, –2.27 to –0.61), the Alzheimer’s Disease Composite Score (mean difference, –0.05; 95% CI, –.074 to –.027,), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment score (mean difference, 2.0; 95% CI, 1.2-2.8; all, P < .001).

Overall, Dr. van Dyck said, “Lecanemab met the primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months.”

In a substudy of 698 participants, results showed that amyloid burden fell at a higher rate in the lecanemab group than in the placebo group (difference, –59.1 centiloids; 95% CI, –62.6 to –55.6).

“Lecanemab has high selectivity for soluble aggregated species of A-beta as compared with monomeric amyloid, with moderate selectivity for fibrillar amyloid; this profile is considered to target the most toxic pathologic amyloid species,” the researchers wrote.
 

Concerning AE data

With respect to AEs, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, according to a report in the journal Science published Nov. 27, a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Researchers summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

In a CTAD presentation, study coauthor Marwan Sabbagh, MD, Barrow Neurological Institute, Phoenix, said two hemorrhage-related deaths occurred in an open-label extension. One was in the context of a tissue plasminogen activator treatment for a stroke, which fits with the description of the case in the Science report. “Causality with lecanemab is a little difficult ...,” he said. “Patients on anticoagulation might need further consideration.”

In the CLARITY AD Trial, serious AEs occurred in 14% of the lecanemab group, leading to discontinuation 6.9% of the time, and in 11.3% of the placebo group, leading to discontinuation 2.9% of the time, the investigators reported.

They added that, in the lecanemab group, the most common AEs, defined as affecting more than 10% of participants, were infusion-related reactions (26.4% vs. 7.4% for placebo); amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (17.3% vs. 9%, respectively); amyloid-related imaging abnormalities with edema or effusions (12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% vs. 9.6%).

In addition, macrohemorrhage was reported in 0.6% of the lecanemab group and 0.1% of the placebo group.
 

Cautious optimism

In separate interviews, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive, owing to the large investment needed for research, he added, and patients will have to undergo costly testing, such as PET scans and spinal taps.

Still, “this could be a valuable adjunct to the armamentarium we have,” which includes interventions such as lifestyle changes, he said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and that the drug had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially among patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal – fully reversing cognitive decline.

Michael Weiner, MD, president of the CTAD22 Scientific Committee, noted in a press release that there is “growing evidence” that some antiamyloid therapies, “especially lecanemab and donanemab” have shown promising results.

“Unfortunately, these treatments are also associated with abnormal differences seen in imaging, including brain swelling and bleeding in the brain,” said Dr. Weiner, professor of radiology, medicine, and neurology at the University of California, San Francisco.

“There is considerable controversy concerning the significance and impact of these findings, including whether or not governments and medical insurance will provide financial coverage for such treatments,” he added.
 

Rave reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared that the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease ...” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is a staunch supporter of aducanumab, called on the Centers for Medicare & Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the two reported deaths.

The trial was supported by Eisai (regulatory sponsor) with partial funding from Biogen. Dr. van Dyck reports having received research grants from Biogen, Eisai, Biohaven, Cerevel Therapeutics, Eli Lilly, Genentech, Janssen, Novartis, and UCB. He has been a consultant to Cerevel, Eisai, Ono Pharmaceutical, and Roche. Relevant financial relationships for the other investigators are fully listed in the original article.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Widely anticipated data from a phase 3 trial of the monoclonal antibody lecanemab suggest the drug “modestly” relieved cognitive impairment in patients with early Alzheimer’s disease (AD) – but at a cost.

In the CLARITY AD trial, adverse events (AEs) were common compared with placebo, including amyloid-related edema and effusions; and a recent news report linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” wrote Christopher H. van Dyck, MD, Yale University, New Haven, Conn., and colleagues.

The full trial findings were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, with simultaneous publication on Nov. 29 in the New England Journal of Medicine.
 

Complications in the field

The phase 3 trial of lecanemab has been closely watched in AD circles, especially considering positive early data released in September and reported by this news organization at that time.

The Food and Drug Administration is expected to make a decision about possible approval of the drug in January 2023. Only one other antiamyloid treatment, the highly controversial and expensive aducanumab (Aduhelm), is currently approved by the FDA.

For the new 18-month, randomized, double-blind CLARITY AD trial, researchers enrolled 1,795 patients aged 50-90 years (average age, 71 years) with early AD. All were randomly assigned to receive either a placebo (n = 898) or intravenous lecanemab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets amyloid beta (A-beta) protofibrils, at 10 mg/kg of body weight every 2 weeks (n = 897).

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. Safety data included all participants, and the modified intention-to-treat group included 1,734 participants, with 859 receiving lecanemab and 875 receiving placebo.

The primary endpoint was the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Scores from 0.5 to 6 are signs of early AD, according to the study. The mean baseline score for both groups was 3.2. The adjusted mean change at 18 months was 1.21 for lecanemab versus 1.66 for placebo (difference, –0.45; 95% confidence interval [CI], –0.67 to –0.23; P < .001).

As Dr. van Dyck noted in his presentation at the CTAD meting, this represents a 27% slowing of the decline in the lecanemab group.

The published findings do not speculate about how this difference would affect the day-to-day life of participants who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Other measurements that suggest cognitive improvements in the lecanemab group versus placebo include the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score (mean difference, –1.44; 95% CI, –2.27 to –0.61), the Alzheimer’s Disease Composite Score (mean difference, –0.05; 95% CI, –.074 to –.027,), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment score (mean difference, 2.0; 95% CI, 1.2-2.8; all, P < .001).

Overall, Dr. van Dyck said, “Lecanemab met the primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months.”

In a substudy of 698 participants, results showed that amyloid burden fell at a higher rate in the lecanemab group than in the placebo group (difference, –59.1 centiloids; 95% CI, –62.6 to –55.6).

“Lecanemab has high selectivity for soluble aggregated species of A-beta as compared with monomeric amyloid, with moderate selectivity for fibrillar amyloid; this profile is considered to target the most toxic pathologic amyloid species,” the researchers wrote.
 

Concerning AE data

With respect to AEs, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, according to a report in the journal Science published Nov. 27, a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Researchers summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

In a CTAD presentation, study coauthor Marwan Sabbagh, MD, Barrow Neurological Institute, Phoenix, said two hemorrhage-related deaths occurred in an open-label extension. One was in the context of a tissue plasminogen activator treatment for a stroke, which fits with the description of the case in the Science report. “Causality with lecanemab is a little difficult ...,” he said. “Patients on anticoagulation might need further consideration.”

In the CLARITY AD Trial, serious AEs occurred in 14% of the lecanemab group, leading to discontinuation 6.9% of the time, and in 11.3% of the placebo group, leading to discontinuation 2.9% of the time, the investigators reported.

They added that, in the lecanemab group, the most common AEs, defined as affecting more than 10% of participants, were infusion-related reactions (26.4% vs. 7.4% for placebo); amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (17.3% vs. 9%, respectively); amyloid-related imaging abnormalities with edema or effusions (12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% vs. 9.6%).

In addition, macrohemorrhage was reported in 0.6% of the lecanemab group and 0.1% of the placebo group.
 

Cautious optimism

In separate interviews, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive, owing to the large investment needed for research, he added, and patients will have to undergo costly testing, such as PET scans and spinal taps.

Still, “this could be a valuable adjunct to the armamentarium we have,” which includes interventions such as lifestyle changes, he said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and that the drug had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially among patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal – fully reversing cognitive decline.

Michael Weiner, MD, president of the CTAD22 Scientific Committee, noted in a press release that there is “growing evidence” that some antiamyloid therapies, “especially lecanemab and donanemab” have shown promising results.

“Unfortunately, these treatments are also associated with abnormal differences seen in imaging, including brain swelling and bleeding in the brain,” said Dr. Weiner, professor of radiology, medicine, and neurology at the University of California, San Francisco.

“There is considerable controversy concerning the significance and impact of these findings, including whether or not governments and medical insurance will provide financial coverage for such treatments,” he added.
 

Rave reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared that the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease ...” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is a staunch supporter of aducanumab, called on the Centers for Medicare & Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the two reported deaths.

The trial was supported by Eisai (regulatory sponsor) with partial funding from Biogen. Dr. van Dyck reports having received research grants from Biogen, Eisai, Biohaven, Cerevel Therapeutics, Eli Lilly, Genentech, Janssen, Novartis, and UCB. He has been a consultant to Cerevel, Eisai, Ono Pharmaceutical, and Roche. Relevant financial relationships for the other investigators are fully listed in the original article.

A version of this article first appeared on Medscape.com.

CHICAGO – Taking NSAIDs for knee osteoarthritis may worsen inflammation and pain over time, suggest new data revealed at the annual meeting of the Radiological Society of North America.

Johanna Luitjens, MD, a postdoctoral scholar in the department of radiology and biomedical Imaging at the University of California, San Francisco, told this news organization that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help – and may actually worsen – outcomes.

Denise Fulton/MDedge News

In particular, this study looked at the impact of NSAIDs on synovitis – the inflammation of the membrane lining the knee joint – by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.
 

No approved therapy to reduce OA progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

Dr. Luitjens noted, however, that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Dr. Luitjens and associates studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID, compared with controls (adjusted difference in score, 0.26; 95% confidence interval, –0.5 to –0.129; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (adjusted difference in score, 0.46; 95% CI, 0.2-0.72; P < .001) and higher increase in effusion synovitis (adjusted difference in score, 0.27; 95% CI, 0.06-0.47;  P = .01) in NSAID users, compared with controls.

IFP size and synovial proliferation score did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up.

Design limits strength

Amanda E. Nelson, MD, associate professor of medicine, division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr. Nelson was not involved in the OAI or Dr. Luitjens’ analysis.)

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she said in an interview. Without randomization, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said, adding that the effect sizes were small.

Measures such as the IFP are ranked 0-3, so “the clinical difference of a 0.26 difference on a 0-3 scale is a bit uncertain,” she said.

Dr. Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the risks in older adults

Una Makris, MD, associate professor of internal medicine in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, noted that NSAIDs are “not always the safest option.”

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Dr. Makris, who was not involved in the study, told this news organization.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks – including known adverse effects which can be amplified in older adults – and benefits with the goal of improved function and less pain,” Dr. Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Dr. Luitjens, Dr. Nelson, and Dr. Makris reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHICAGO – Taking NSAIDs for knee osteoarthritis may worsen inflammation and pain over time, suggest new data revealed at the annual meeting of the Radiological Society of North America.

Johanna Luitjens, MD, a postdoctoral scholar in the department of radiology and biomedical Imaging at the University of California, San Francisco, told this news organization that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help – and may actually worsen – outcomes.

Denise Fulton/MDedge News

In particular, this study looked at the impact of NSAIDs on synovitis – the inflammation of the membrane lining the knee joint – by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.
 

No approved therapy to reduce OA progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

Dr. Luitjens noted, however, that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Dr. Luitjens and associates studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID, compared with controls (adjusted difference in score, 0.26; 95% confidence interval, –0.5 to –0.129; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (adjusted difference in score, 0.46; 95% CI, 0.2-0.72; P < .001) and higher increase in effusion synovitis (adjusted difference in score, 0.27; 95% CI, 0.06-0.47;  P = .01) in NSAID users, compared with controls.

IFP size and synovial proliferation score did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up.

Design limits strength

Amanda E. Nelson, MD, associate professor of medicine, division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr. Nelson was not involved in the OAI or Dr. Luitjens’ analysis.)

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she said in an interview. Without randomization, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said, adding that the effect sizes were small.

Measures such as the IFP are ranked 0-3, so “the clinical difference of a 0.26 difference on a 0-3 scale is a bit uncertain,” she said.

Dr. Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the risks in older adults

Una Makris, MD, associate professor of internal medicine in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, noted that NSAIDs are “not always the safest option.”

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Dr. Makris, who was not involved in the study, told this news organization.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks – including known adverse effects which can be amplified in older adults – and benefits with the goal of improved function and less pain,” Dr. Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Dr. Luitjens, Dr. Nelson, and Dr. Makris reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHICAGO – Taking NSAIDs for knee osteoarthritis may worsen inflammation and pain over time, suggest new data revealed at the annual meeting of the Radiological Society of North America.

Johanna Luitjens, MD, a postdoctoral scholar in the department of radiology and biomedical Imaging at the University of California, San Francisco, told this news organization that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help – and may actually worsen – outcomes.

Denise Fulton/MDedge News

In particular, this study looked at the impact of NSAIDs on synovitis – the inflammation of the membrane lining the knee joint – by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.
 

No approved therapy to reduce OA progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

Dr. Luitjens noted, however, that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Dr. Luitjens and associates studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID, compared with controls (adjusted difference in score, 0.26; 95% confidence interval, –0.5 to –0.129; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (adjusted difference in score, 0.46; 95% CI, 0.2-0.72; P < .001) and higher increase in effusion synovitis (adjusted difference in score, 0.27; 95% CI, 0.06-0.47;  P = .01) in NSAID users, compared with controls.

IFP size and synovial proliferation score did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up.

Design limits strength

Amanda E. Nelson, MD, associate professor of medicine, division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr. Nelson was not involved in the OAI or Dr. Luitjens’ analysis.)

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she said in an interview. Without randomization, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said, adding that the effect sizes were small.

Measures such as the IFP are ranked 0-3, so “the clinical difference of a 0.26 difference on a 0-3 scale is a bit uncertain,” she said.

Dr. Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the risks in older adults

Una Makris, MD, associate professor of internal medicine in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, noted that NSAIDs are “not always the safest option.”

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Dr. Makris, who was not involved in the study, told this news organization.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks – including known adverse effects which can be amplified in older adults – and benefits with the goal of improved function and less pain,” Dr. Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Dr. Luitjens, Dr. Nelson, and Dr. Makris reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

DENVER – As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

DENVER – As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

DENVER – As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

Nano-pulse stimulation has emerged as a promising treatment option for sebaceous hyperplasia, warts, and other dermal lesions without the use of heat.

During a virtual course on laser and aesthetic skin therapy, Yakir Levin, MD, PhD, likened nano-pulse stimulation to microneedling or radiofrequency microneedling “in that you have an array of microneedles that go into the skin,” he said. “However, it is actually completely different.”

The CellFX System uses nano-pulse stimulation to deliver ultrashort electrical energy pulses into the skin of target lesions via a console-based handheld applicator. In September 2022, the Food and Drug Administration cleared the CellFX system for treatment of sebaceous hyperplasia in patients with Fitzpatrick skin types I-II. This followed a general clearance of the device in 2021 for dermatologic procedures requiring ablation and resurfacing of the skin.

Pulses from the device deliver a “constant electrical potential gradient across cell membranes and organelle membranes, causing them to break down,” explained Dr. Levin, a dermatologist and physician scientist at Massachusetts General Hospital, Boston, where he practices cosmetic dermatology and conducts research on birthmarks in children. This creates pores in those membranes “and leads to a controlled form of cell death,” he said. “As a result, this treatment is limited to cells, so you can do it in the dermis without damaging the collagen network. It spares tissue that’s outside of the field, and it’s nonthermal.”

Images from electron microscopy have demonstrated swelling of the mitochondria and breakdown of nuclei within 2 hours of treatment in a rat study. “Within 1 day of treatment you have death of the cells and the beginning of involution of the lesion,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “This presents us with the opportunity to treat dermal lesions without causing damage to the epidermis or to the acellular portion of the dermis.”

In published studies, nano-pulse stimulation has been shown to be effective for treating sebaceous hyperplasia and warts. According to Dr. Levin, clinicians typically treat sebaceous hyperplasia with an radiofrequency microneedle or electrodesiccation, “where we shave off the top but do not try to hit the bottom because we don’t want to cause scarring of the dermis,” he said. “Using the nano-pulse stimulation technology, however, you end up with involution of the sebaceous lesion without damaging the surrounding dermis.”

In a prospective, randomized study, 72 individuals with sebaceous gland hyperplasia received nano-pulse stimulation to 222 lesions and they returned for three to four follow-up evaluations with photographs. At the final study visit, investigators rated 99.6% of the sebaceous gland lesions as clear or mostly clear, while 79% of the study participants said they were “satisfied” or “mostly satisfied” with the outcome.

At posttreatment day 60, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild posttreatment hyperpigmentation.

In a more recent study, researchers used the CellFX System to treat 195 cutaneous warts up to 10 mm wide in 62 individuals enrolled at one of five sites. They found that 75% of common warts, 73% of flat warts, and 44% of plantar warts were completely clear 60 days following the last nano-pulse stimulation treatment and did not recur within the 120-day observation period.

The most common reactions at the treatment sites were erythema (51%) and eschar formation (23%) on day 30.

According to Dr. Levin, promising future applications of nano-pulse stimulation include treatment of syringomas, dermatofibromas, and basal cell carcinomas.

Dr. Levin reported financial interest in Accure Acne, Avava Medical, and Soltego. The CellFX system was developed and is marketed by Pulse Biosciences.

Nano-pulse stimulation has emerged as a promising treatment option for sebaceous hyperplasia, warts, and other dermal lesions without the use of heat.

During a virtual course on laser and aesthetic skin therapy, Yakir Levin, MD, PhD, likened nano-pulse stimulation to microneedling or radiofrequency microneedling “in that you have an array of microneedles that go into the skin,” he said. “However, it is actually completely different.”

The CellFX System uses nano-pulse stimulation to deliver ultrashort electrical energy pulses into the skin of target lesions via a console-based handheld applicator. In September 2022, the Food and Drug Administration cleared the CellFX system for treatment of sebaceous hyperplasia in patients with Fitzpatrick skin types I-II. This followed a general clearance of the device in 2021 for dermatologic procedures requiring ablation and resurfacing of the skin.

Pulses from the device deliver a “constant electrical potential gradient across cell membranes and organelle membranes, causing them to break down,” explained Dr. Levin, a dermatologist and physician scientist at Massachusetts General Hospital, Boston, where he practices cosmetic dermatology and conducts research on birthmarks in children. This creates pores in those membranes “and leads to a controlled form of cell death,” he said. “As a result, this treatment is limited to cells, so you can do it in the dermis without damaging the collagen network. It spares tissue that’s outside of the field, and it’s nonthermal.”

Images from electron microscopy have demonstrated swelling of the mitochondria and breakdown of nuclei within 2 hours of treatment in a rat study. “Within 1 day of treatment you have death of the cells and the beginning of involution of the lesion,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “This presents us with the opportunity to treat dermal lesions without causing damage to the epidermis or to the acellular portion of the dermis.”

In published studies, nano-pulse stimulation has been shown to be effective for treating sebaceous hyperplasia and warts. According to Dr. Levin, clinicians typically treat sebaceous hyperplasia with an radiofrequency microneedle or electrodesiccation, “where we shave off the top but do not try to hit the bottom because we don’t want to cause scarring of the dermis,” he said. “Using the nano-pulse stimulation technology, however, you end up with involution of the sebaceous lesion without damaging the surrounding dermis.”

In a prospective, randomized study, 72 individuals with sebaceous gland hyperplasia received nano-pulse stimulation to 222 lesions and they returned for three to four follow-up evaluations with photographs. At the final study visit, investigators rated 99.6% of the sebaceous gland lesions as clear or mostly clear, while 79% of the study participants said they were “satisfied” or “mostly satisfied” with the outcome.

At posttreatment day 60, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild posttreatment hyperpigmentation.

In a more recent study, researchers used the CellFX System to treat 195 cutaneous warts up to 10 mm wide in 62 individuals enrolled at one of five sites. They found that 75% of common warts, 73% of flat warts, and 44% of plantar warts were completely clear 60 days following the last nano-pulse stimulation treatment and did not recur within the 120-day observation period.

The most common reactions at the treatment sites were erythema (51%) and eschar formation (23%) on day 30.

According to Dr. Levin, promising future applications of nano-pulse stimulation include treatment of syringomas, dermatofibromas, and basal cell carcinomas.

Dr. Levin reported financial interest in Accure Acne, Avava Medical, and Soltego. The CellFX system was developed and is marketed by Pulse Biosciences.

Nano-pulse stimulation has emerged as a promising treatment option for sebaceous hyperplasia, warts, and other dermal lesions without the use of heat.

During a virtual course on laser and aesthetic skin therapy, Yakir Levin, MD, PhD, likened nano-pulse stimulation to microneedling or radiofrequency microneedling “in that you have an array of microneedles that go into the skin,” he said. “However, it is actually completely different.”

The CellFX System uses nano-pulse stimulation to deliver ultrashort electrical energy pulses into the skin of target lesions via a console-based handheld applicator. In September 2022, the Food and Drug Administration cleared the CellFX system for treatment of sebaceous hyperplasia in patients with Fitzpatrick skin types I-II. This followed a general clearance of the device in 2021 for dermatologic procedures requiring ablation and resurfacing of the skin.

Pulses from the device deliver a “constant electrical potential gradient across cell membranes and organelle membranes, causing them to break down,” explained Dr. Levin, a dermatologist and physician scientist at Massachusetts General Hospital, Boston, where he practices cosmetic dermatology and conducts research on birthmarks in children. This creates pores in those membranes “and leads to a controlled form of cell death,” he said. “As a result, this treatment is limited to cells, so you can do it in the dermis without damaging the collagen network. It spares tissue that’s outside of the field, and it’s nonthermal.”

Images from electron microscopy have demonstrated swelling of the mitochondria and breakdown of nuclei within 2 hours of treatment in a rat study. “Within 1 day of treatment you have death of the cells and the beginning of involution of the lesion,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “This presents us with the opportunity to treat dermal lesions without causing damage to the epidermis or to the acellular portion of the dermis.”

In published studies, nano-pulse stimulation has been shown to be effective for treating sebaceous hyperplasia and warts. According to Dr. Levin, clinicians typically treat sebaceous hyperplasia with an radiofrequency microneedle or electrodesiccation, “where we shave off the top but do not try to hit the bottom because we don’t want to cause scarring of the dermis,” he said. “Using the nano-pulse stimulation technology, however, you end up with involution of the sebaceous lesion without damaging the surrounding dermis.”

In a prospective, randomized study, 72 individuals with sebaceous gland hyperplasia received nano-pulse stimulation to 222 lesions and they returned for three to four follow-up evaluations with photographs. At the final study visit, investigators rated 99.6% of the sebaceous gland lesions as clear or mostly clear, while 79% of the study participants said they were “satisfied” or “mostly satisfied” with the outcome.

At posttreatment day 60, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild posttreatment hyperpigmentation.

In a more recent study, researchers used the CellFX System to treat 195 cutaneous warts up to 10 mm wide in 62 individuals enrolled at one of five sites. They found that 75% of common warts, 73% of flat warts, and 44% of plantar warts were completely clear 60 days following the last nano-pulse stimulation treatment and did not recur within the 120-day observation period.

The most common reactions at the treatment sites were erythema (51%) and eschar formation (23%) on day 30.

According to Dr. Levin, promising future applications of nano-pulse stimulation include treatment of syringomas, dermatofibromas, and basal cell carcinomas.

Dr. Levin reported financial interest in Accure Acne, Avava Medical, and Soltego. The CellFX system was developed and is marketed by Pulse Biosciences.

In human papillomavirus (HPV)-positive, locally advanced oropharyngeal squamous cell carcinoma, an immune checkpoint blockade regimen combined with radiotherapy led to good survival with a reduction in radiation exposure.

First-line therapy for HPV-positive oropharynx cancer is generally high-dose cisplatin combined with high-dose radiotherapy, but this regimen is associated with significant acute and long-term toxicity.

In previous studies among patients with recurrent or metastatic squamous cell carcinoma, nivolumab (Opdiva, Bristol Myers Squibb) improved survival when combined with platinum-based chemotherapy, and pembrolizumab (Keytruda, Merck) improved survival in recurrent disease compared with chemotherapy plus cetuximab.

Those precedents predicted success for HPV-positive oropharynx cancer, according to Maura Gillison, MD, PhD, who presented the results at a press briefing held in November in advance of the Society for Immunotherapy of Cancer’s 37th Annual Meeting. “Given that HPV-positive oropharynx cancers are characterized by an inflamed tumor microenvironment and HPV oncoproteins are omnipresent, required for cancer survival, and are ideal tumor-specific antigens – we hypothesized that induction and concurrent CTLA-4 and PD-1 immune checkpoint blockade, followed by volume- and dose-adapted IMRT (intensity-modulated radiotherapy), would be an effective alternative to the current standard of care,” said Dr. Gillison, who is a professor of medicine at the University of Texas MD Anderson Cancer Center, Houston.

Anti–PD-L1 therapy is approved for head and neck cancer, but the frontier is moving it into the locally advanced setting in combination with CTLA-4 inhibitors, according to Robert Ferris, MD, PhD, who moderated the press briefing and was lead author of the nivolumab in metastatic squamous cell carcinoma study. He added that recent trial data suggest this approach should be more effective and create more durable responses.

The new data support the approach. “The trial provides compelling data to support a new approach for treating newly diagnosed HPV-positive head and neck cancers. Our goal is to treat this cancer with immunotherapy alone. The results of this trial make me optimistic that this will be achievable,” Dr. Gillison said.
 

The study details

The researchers conducted a phase 2 clinical trial, enrolling 35 patients with newly diagnosed HPV-positive oropharynx cancer who were positive for PD-L1 expression.

Patients received 1 mg/kg ipilimumab (Yervoy, Bristol Myers Squibb) and 3 mg/kg nivolumab over a 6-week cycle, followed by a second cycle that was accompanied by 40-44 Gy radiotherapy for patients with a complete response in their primary tumor, and a boost to 50-66 based on postinduction treatment volume. The protocol reduced dose to the neck from 52 to 36 Gy. The radiation was delivered to only one nodal echelon beyond the involved node. Standard care delivers radiotherapy to essentially the entire neck, Dr. Gillison said.

Grade 3 or higher adverse events occurred in 66% of patients, the majority of which were attributable to radiotherapy. The complete response rate was 94% at 6 months as assessed by PET scan, and 2-year progression-free survival was 86%. After a median follow-up of 14.9 months, all patients were alive and cancer-free.

Overall response rate was 14% following induction, but 96% showed a histologic treatment effect. Tumor viability was less than 5% in 48% of patients, and a molecular complete response was observed in 30% as measured by plasma cell-free HPV. Patients received 36% less radiation than typical of standard of care, and the dose to critical areas was reduced by 50%.

At the press conference, Dr. Ferris asked Dr. Gillison whether the researchers observed a spike in cell-free HPV DNA before the decline occurred, suggesting evidence of tumor death and DNA release.

“We did see in a remarkable number of patients within 2 weeks of the first dose, a very strong peak in the cell-free HPV DNA, followed by a rapid decline. In those patients who still have viable tumor at the end of induction immunotherapy, we saw a second robust peak in cell-free HPV DNA at the start of radiation, with rapid clearance. So that gave us confidence that (among) those patients who had cell-free HPV clearance by the end of induction, followed by no further detection through radiation, that it’s an excellent surrogate for tumor control,” Dr. Gillison said.

Dr. Gillison has financial relationships with Eisai, Exilixis, Caladrius, iTeos, Istari, Seagen, Sensei, Bicara, Mirati, Coherus, Debiopharm, Kura, Shattuck, Nektar, Ipsen, EMD Serono, Gilead, LXS, BioNTech, Merck, Bristol Myers Squibb, Bayer, Roche, Genocea, NewLink Genetics, Aspyrian, TRM Oncology, Amgen, AstraZeneca, Celgene, and Agenus. Dr. Ferris has financial relationships with Bristol Myers Squibb, AstraZeneca/MedImmune, Merck, and Celgene.

In human papillomavirus (HPV)-positive, locally advanced oropharyngeal squamous cell carcinoma, an immune checkpoint blockade regimen combined with radiotherapy led to good survival with a reduction in radiation exposure.

First-line therapy for HPV-positive oropharynx cancer is generally high-dose cisplatin combined with high-dose radiotherapy, but this regimen is associated with significant acute and long-term toxicity.

In previous studies among patients with recurrent or metastatic squamous cell carcinoma, nivolumab (Opdiva, Bristol Myers Squibb) improved survival when combined with platinum-based chemotherapy, and pembrolizumab (Keytruda, Merck) improved survival in recurrent disease compared with chemotherapy plus cetuximab.

Those precedents predicted success for HPV-positive oropharynx cancer, according to Maura Gillison, MD, PhD, who presented the results at a press briefing held in November in advance of the Society for Immunotherapy of Cancer’s 37th Annual Meeting. “Given that HPV-positive oropharynx cancers are characterized by an inflamed tumor microenvironment and HPV oncoproteins are omnipresent, required for cancer survival, and are ideal tumor-specific antigens – we hypothesized that induction and concurrent CTLA-4 and PD-1 immune checkpoint blockade, followed by volume- and dose-adapted IMRT (intensity-modulated radiotherapy), would be an effective alternative to the current standard of care,” said Dr. Gillison, who is a professor of medicine at the University of Texas MD Anderson Cancer Center, Houston.

Anti–PD-L1 therapy is approved for head and neck cancer, but the frontier is moving it into the locally advanced setting in combination with CTLA-4 inhibitors, according to Robert Ferris, MD, PhD, who moderated the press briefing and was lead author of the nivolumab in metastatic squamous cell carcinoma study. He added that recent trial data suggest this approach should be more effective and create more durable responses.

The new data support the approach. “The trial provides compelling data to support a new approach for treating newly diagnosed HPV-positive head and neck cancers. Our goal is to treat this cancer with immunotherapy alone. The results of this trial make me optimistic that this will be achievable,” Dr. Gillison said.
 

The study details

The researchers conducted a phase 2 clinical trial, enrolling 35 patients with newly diagnosed HPV-positive oropharynx cancer who were positive for PD-L1 expression.

Patients received 1 mg/kg ipilimumab (Yervoy, Bristol Myers Squibb) and 3 mg/kg nivolumab over a 6-week cycle, followed by a second cycle that was accompanied by 40-44 Gy radiotherapy for patients with a complete response in their primary tumor, and a boost to 50-66 based on postinduction treatment volume. The protocol reduced dose to the neck from 52 to 36 Gy. The radiation was delivered to only one nodal echelon beyond the involved node. Standard care delivers radiotherapy to essentially the entire neck, Dr. Gillison said.

Grade 3 or higher adverse events occurred in 66% of patients, the majority of which were attributable to radiotherapy. The complete response rate was 94% at 6 months as assessed by PET scan, and 2-year progression-free survival was 86%. After a median follow-up of 14.9 months, all patients were alive and cancer-free.

Overall response rate was 14% following induction, but 96% showed a histologic treatment effect. Tumor viability was less than 5% in 48% of patients, and a molecular complete response was observed in 30% as measured by plasma cell-free HPV. Patients received 36% less radiation than typical of standard of care, and the dose to critical areas was reduced by 50%.

At the press conference, Dr. Ferris asked Dr. Gillison whether the researchers observed a spike in cell-free HPV DNA before the decline occurred, suggesting evidence of tumor death and DNA release.

“We did see in a remarkable number of patients within 2 weeks of the first dose, a very strong peak in the cell-free HPV DNA, followed by a rapid decline. In those patients who still have viable tumor at the end of induction immunotherapy, we saw a second robust peak in cell-free HPV DNA at the start of radiation, with rapid clearance. So that gave us confidence that (among) those patients who had cell-free HPV clearance by the end of induction, followed by no further detection through radiation, that it’s an excellent surrogate for tumor control,” Dr. Gillison said.

Dr. Gillison has financial relationships with Eisai, Exilixis, Caladrius, iTeos, Istari, Seagen, Sensei, Bicara, Mirati, Coherus, Debiopharm, Kura, Shattuck, Nektar, Ipsen, EMD Serono, Gilead, LXS, BioNTech, Merck, Bristol Myers Squibb, Bayer, Roche, Genocea, NewLink Genetics, Aspyrian, TRM Oncology, Amgen, AstraZeneca, Celgene, and Agenus. Dr. Ferris has financial relationships with Bristol Myers Squibb, AstraZeneca/MedImmune, Merck, and Celgene.

In human papillomavirus (HPV)-positive, locally advanced oropharyngeal squamous cell carcinoma, an immune checkpoint blockade regimen combined with radiotherapy led to good survival with a reduction in radiation exposure.

First-line therapy for HPV-positive oropharynx cancer is generally high-dose cisplatin combined with high-dose radiotherapy, but this regimen is associated with significant acute and long-term toxicity.

In previous studies among patients with recurrent or metastatic squamous cell carcinoma, nivolumab (Opdiva, Bristol Myers Squibb) improved survival when combined with platinum-based chemotherapy, and pembrolizumab (Keytruda, Merck) improved survival in recurrent disease compared with chemotherapy plus cetuximab.

Those precedents predicted success for HPV-positive oropharynx cancer, according to Maura Gillison, MD, PhD, who presented the results at a press briefing held in November in advance of the Society for Immunotherapy of Cancer’s 37th Annual Meeting. “Given that HPV-positive oropharynx cancers are characterized by an inflamed tumor microenvironment and HPV oncoproteins are omnipresent, required for cancer survival, and are ideal tumor-specific antigens – we hypothesized that induction and concurrent CTLA-4 and PD-1 immune checkpoint blockade, followed by volume- and dose-adapted IMRT (intensity-modulated radiotherapy), would be an effective alternative to the current standard of care,” said Dr. Gillison, who is a professor of medicine at the University of Texas MD Anderson Cancer Center, Houston.

Anti–PD-L1 therapy is approved for head and neck cancer, but the frontier is moving it into the locally advanced setting in combination with CTLA-4 inhibitors, according to Robert Ferris, MD, PhD, who moderated the press briefing and was lead author of the nivolumab in metastatic squamous cell carcinoma study. He added that recent trial data suggest this approach should be more effective and create more durable responses.

The new data support the approach. “The trial provides compelling data to support a new approach for treating newly diagnosed HPV-positive head and neck cancers. Our goal is to treat this cancer with immunotherapy alone. The results of this trial make me optimistic that this will be achievable,” Dr. Gillison said.
 

The study details

The researchers conducted a phase 2 clinical trial, enrolling 35 patients with newly diagnosed HPV-positive oropharynx cancer who were positive for PD-L1 expression.

Patients received 1 mg/kg ipilimumab (Yervoy, Bristol Myers Squibb) and 3 mg/kg nivolumab over a 6-week cycle, followed by a second cycle that was accompanied by 40-44 Gy radiotherapy for patients with a complete response in their primary tumor, and a boost to 50-66 based on postinduction treatment volume. The protocol reduced dose to the neck from 52 to 36 Gy. The radiation was delivered to only one nodal echelon beyond the involved node. Standard care delivers radiotherapy to essentially the entire neck, Dr. Gillison said.

Grade 3 or higher adverse events occurred in 66% of patients, the majority of which were attributable to radiotherapy. The complete response rate was 94% at 6 months as assessed by PET scan, and 2-year progression-free survival was 86%. After a median follow-up of 14.9 months, all patients were alive and cancer-free.

Overall response rate was 14% following induction, but 96% showed a histologic treatment effect. Tumor viability was less than 5% in 48% of patients, and a molecular complete response was observed in 30% as measured by plasma cell-free HPV. Patients received 36% less radiation than typical of standard of care, and the dose to critical areas was reduced by 50%.

At the press conference, Dr. Ferris asked Dr. Gillison whether the researchers observed a spike in cell-free HPV DNA before the decline occurred, suggesting evidence of tumor death and DNA release.

“We did see in a remarkable number of patients within 2 weeks of the first dose, a very strong peak in the cell-free HPV DNA, followed by a rapid decline. In those patients who still have viable tumor at the end of induction immunotherapy, we saw a second robust peak in cell-free HPV DNA at the start of radiation, with rapid clearance. So that gave us confidence that (among) those patients who had cell-free HPV clearance by the end of induction, followed by no further detection through radiation, that it’s an excellent surrogate for tumor control,” Dr. Gillison said.

Dr. Gillison has financial relationships with Eisai, Exilixis, Caladrius, iTeos, Istari, Seagen, Sensei, Bicara, Mirati, Coherus, Debiopharm, Kura, Shattuck, Nektar, Ipsen, EMD Serono, Gilead, LXS, BioNTech, Merck, Bristol Myers Squibb, Bayer, Roche, Genocea, NewLink Genetics, Aspyrian, TRM Oncology, Amgen, AstraZeneca, Celgene, and Agenus. Dr. Ferris has financial relationships with Bristol Myers Squibb, AstraZeneca/MedImmune, Merck, and Celgene.

Latinx individuals have a lower overall risk of melanoma than non-Latinx Whites (NLW), but they are more likely to be diagnosed with advanced disease, and experience greater mortality. A new qualitative study of Latinx and low-income NLW individuals in California has revealed some of the socioeconomic and community factors that may play a role in preventing early access to care.

Thicker melanomas, which are more likely to be lethal, are on the rise in the United States among people with lower socioeconomic status (SES), as well as African Americans and Hispanics, and both Black and Latinx people are more likely than NLW people to present with stage 3 or stage 4 disease. “That has really prompted us to look at community engagement and outreach and then really understand the qualitative aspects that are driving individuals into higher risk for melanoma, apart from just limited insurance and access to health care,” said Susan Swetter, MD, who presented the results of the study at the annual meeting of the American Society of Clinical Oncology.

Other studies, such as a Boston-area survey published in 2020, suggest that Hispanics are less likely than Whites to know the meaning of the term melanoma (odds ratio, 0.27; P =.0037), suggesting the need for educational efforts. The authors of that study noted that knowledge of melanoma in 2017, when the survey was conducted, remained essentially unchanged since a previous study was published in 1996.

“Our results support a need for better public educational programs, particularly those geared toward minority populations. Educational programs that are culturally relevant and include specific sections for skin of color have been shown to better promote early melanoma detection in individuals of ethnic minorities and may help decrease the ethnic disparities in melanoma-related mortality. At the patient-physician level, dermatologists may educate their patients, including Hispanic patients, should they choose to perform (skin self-examinations) to specifically inspect the extremities and acral areas, given the higher incidence rates of melanoma on those areas in this population,” the authors wrote.

The goal of the new study is to get a better understanding of the factors that affect attitudes toward health care, and the researchers found a complex mixture that including ethnicity, cultural, gender identity, geography, skin color, gender norms, and socioeconomic status (SES). “Qualitative research can inform our preventive and early detection strategies. For instance, in the Latinx group, there’s a lot of mistrust of health systems, medical providers, and who is providing that knowledge. We have to figure out ways to provide a trusted source of information. Doctors and physicians and health providers tend to be trusted, but there are many barriers to getting lower SES patients into care. We’re now investigating the use of community health workers and even individuals in various settings and community centers, religious settings or religious leaders, where we’ve determined through this focus group research that there is increased trust,” Dr. Swetter said.

The researchers assembled 19 focus groups with 176 total adult participants, interviewing them about perceptions of melanoma risk, prevention and screening strategies and their acceptability, and barriers to melanoma prevention and care. The sample include people from urban and semirural areas; 55%-62% of participants self-identified as Latinx or Hispanic and 26%-27% as NLW.

Latinx and semirural participants reported having minimal conversations with family about melanoma prevention, and those who reported having darker skin perceived their risk from skin cancer as lower. Participants who lived in rural areas, were Latinx, or of low SES status indicated that health care access challenges included out-of-pocket costs, past experiences of physicians showing less concern about them, and little confidence that rural physicians had the needed expertise or would make an appropriate referral.

The study is just the first step in a series of efforts to improve melanoma outcomes in high-risk populations, which is being pursued through Stanford University’s Wipe Out Melanoma–California statewide initiative and research consortium. “What we aim to do is use this knowledge to now design programs to reach the populations who are more likely to present with worse disease, and to prevent that disease from happening. These qualitative analyses are few and far between in the world of melanoma, and we’re really happy to really push this envelope and change the way we deliver preventive and early detection efforts,” said Dr. Swetter, who is a professor of dermatology and director of the pigmented lesion/melanoma and cutaneous oncology programs at Stanford (Calif.) University Medical Center. Dr. Swetter also chairs the National Comprehensive Cancer Network guidelines for cutaneous melanoma.

The study could also improve care of advanced melanoma. “There’s clear evidence that many of these patient and SES factors, economic and knowledge barriers are the same when it comes to getting patients with advanced melanoma into appropriate care and on clinical trials, and that’s true across all races and ethnicities,” said Dr. Swetter.

The ultimate goal of these approaches is to give individuals greater “self-efficacy, such that a person feels more competent to manage his or her own health outcomes. One aspect of this approach is the use of novel technology such as smartphone apps that can track moles or help visualize lesions during teledermatology. “I think that the future of melanoma prevention and early detection is bright, especially if we incorporate novel technologies and engage patients and their communities in the effort. It’s a different strategy, as opposed to the top-down approach of physicians imparting knowledge and providing the exam. Increasing community engagement is critical to reaching the populations at highest risk for advanced disease and getting them into care and detection early,” Dr. Swetter said.

Dr. Swetter has no relevant financial disclosures.

Latinx individuals have a lower overall risk of melanoma than non-Latinx Whites (NLW), but they are more likely to be diagnosed with advanced disease, and experience greater mortality. A new qualitative study of Latinx and low-income NLW individuals in California has revealed some of the socioeconomic and community factors that may play a role in preventing early access to care.

Thicker melanomas, which are more likely to be lethal, are on the rise in the United States among people with lower socioeconomic status (SES), as well as African Americans and Hispanics, and both Black and Latinx people are more likely than NLW people to present with stage 3 or stage 4 disease. “That has really prompted us to look at community engagement and outreach and then really understand the qualitative aspects that are driving individuals into higher risk for melanoma, apart from just limited insurance and access to health care,” said Susan Swetter, MD, who presented the results of the study at the annual meeting of the American Society of Clinical Oncology.

Other studies, such as a Boston-area survey published in 2020, suggest that Hispanics are less likely than Whites to know the meaning of the term melanoma (odds ratio, 0.27; P =.0037), suggesting the need for educational efforts. The authors of that study noted that knowledge of melanoma in 2017, when the survey was conducted, remained essentially unchanged since a previous study was published in 1996.

“Our results support a need for better public educational programs, particularly those geared toward minority populations. Educational programs that are culturally relevant and include specific sections for skin of color have been shown to better promote early melanoma detection in individuals of ethnic minorities and may help decrease the ethnic disparities in melanoma-related mortality. At the patient-physician level, dermatologists may educate their patients, including Hispanic patients, should they choose to perform (skin self-examinations) to specifically inspect the extremities and acral areas, given the higher incidence rates of melanoma on those areas in this population,” the authors wrote.

The goal of the new study is to get a better understanding of the factors that affect attitudes toward health care, and the researchers found a complex mixture that including ethnicity, cultural, gender identity, geography, skin color, gender norms, and socioeconomic status (SES). “Qualitative research can inform our preventive and early detection strategies. For instance, in the Latinx group, there’s a lot of mistrust of health systems, medical providers, and who is providing that knowledge. We have to figure out ways to provide a trusted source of information. Doctors and physicians and health providers tend to be trusted, but there are many barriers to getting lower SES patients into care. We’re now investigating the use of community health workers and even individuals in various settings and community centers, religious settings or religious leaders, where we’ve determined through this focus group research that there is increased trust,” Dr. Swetter said.

The researchers assembled 19 focus groups with 176 total adult participants, interviewing them about perceptions of melanoma risk, prevention and screening strategies and their acceptability, and barriers to melanoma prevention and care. The sample include people from urban and semirural areas; 55%-62% of participants self-identified as Latinx or Hispanic and 26%-27% as NLW.

Latinx and semirural participants reported having minimal conversations with family about melanoma prevention, and those who reported having darker skin perceived their risk from skin cancer as lower. Participants who lived in rural areas, were Latinx, or of low SES status indicated that health care access challenges included out-of-pocket costs, past experiences of physicians showing less concern about them, and little confidence that rural physicians had the needed expertise or would make an appropriate referral.

The study is just the first step in a series of efforts to improve melanoma outcomes in high-risk populations, which is being pursued through Stanford University’s Wipe Out Melanoma–California statewide initiative and research consortium. “What we aim to do is use this knowledge to now design programs to reach the populations who are more likely to present with worse disease, and to prevent that disease from happening. These qualitative analyses are few and far between in the world of melanoma, and we’re really happy to really push this envelope and change the way we deliver preventive and early detection efforts,” said Dr. Swetter, who is a professor of dermatology and director of the pigmented lesion/melanoma and cutaneous oncology programs at Stanford (Calif.) University Medical Center. Dr. Swetter also chairs the National Comprehensive Cancer Network guidelines for cutaneous melanoma.

The study could also improve care of advanced melanoma. “There’s clear evidence that many of these patient and SES factors, economic and knowledge barriers are the same when it comes to getting patients with advanced melanoma into appropriate care and on clinical trials, and that’s true across all races and ethnicities,” said Dr. Swetter.

The ultimate goal of these approaches is to give individuals greater “self-efficacy, such that a person feels more competent to manage his or her own health outcomes. One aspect of this approach is the use of novel technology such as smartphone apps that can track moles or help visualize lesions during teledermatology. “I think that the future of melanoma prevention and early detection is bright, especially if we incorporate novel technologies and engage patients and their communities in the effort. It’s a different strategy, as opposed to the top-down approach of physicians imparting knowledge and providing the exam. Increasing community engagement is critical to reaching the populations at highest risk for advanced disease and getting them into care and detection early,” Dr. Swetter said.

Dr. Swetter has no relevant financial disclosures.

Latinx individuals have a lower overall risk of melanoma than non-Latinx Whites (NLW), but they are more likely to be diagnosed with advanced disease, and experience greater mortality. A new qualitative study of Latinx and low-income NLW individuals in California has revealed some of the socioeconomic and community factors that may play a role in preventing early access to care.

Thicker melanomas, which are more likely to be lethal, are on the rise in the United States among people with lower socioeconomic status (SES), as well as African Americans and Hispanics, and both Black and Latinx people are more likely than NLW people to present with stage 3 or stage 4 disease. “That has really prompted us to look at community engagement and outreach and then really understand the qualitative aspects that are driving individuals into higher risk for melanoma, apart from just limited insurance and access to health care,” said Susan Swetter, MD, who presented the results of the study at the annual meeting of the American Society of Clinical Oncology.

Other studies, such as a Boston-area survey published in 2020, suggest that Hispanics are less likely than Whites to know the meaning of the term melanoma (odds ratio, 0.27; P =.0037), suggesting the need for educational efforts. The authors of that study noted that knowledge of melanoma in 2017, when the survey was conducted, remained essentially unchanged since a previous study was published in 1996.

“Our results support a need for better public educational programs, particularly those geared toward minority populations. Educational programs that are culturally relevant and include specific sections for skin of color have been shown to better promote early melanoma detection in individuals of ethnic minorities and may help decrease the ethnic disparities in melanoma-related mortality. At the patient-physician level, dermatologists may educate their patients, including Hispanic patients, should they choose to perform (skin self-examinations) to specifically inspect the extremities and acral areas, given the higher incidence rates of melanoma on those areas in this population,” the authors wrote.

The goal of the new study is to get a better understanding of the factors that affect attitudes toward health care, and the researchers found a complex mixture that including ethnicity, cultural, gender identity, geography, skin color, gender norms, and socioeconomic status (SES). “Qualitative research can inform our preventive and early detection strategies. For instance, in the Latinx group, there’s a lot of mistrust of health systems, medical providers, and who is providing that knowledge. We have to figure out ways to provide a trusted source of information. Doctors and physicians and health providers tend to be trusted, but there are many barriers to getting lower SES patients into care. We’re now investigating the use of community health workers and even individuals in various settings and community centers, religious settings or religious leaders, where we’ve determined through this focus group research that there is increased trust,” Dr. Swetter said.

The researchers assembled 19 focus groups with 176 total adult participants, interviewing them about perceptions of melanoma risk, prevention and screening strategies and their acceptability, and barriers to melanoma prevention and care. The sample include people from urban and semirural areas; 55%-62% of participants self-identified as Latinx or Hispanic and 26%-27% as NLW.

Latinx and semirural participants reported having minimal conversations with family about melanoma prevention, and those who reported having darker skin perceived their risk from skin cancer as lower. Participants who lived in rural areas, were Latinx, or of low SES status indicated that health care access challenges included out-of-pocket costs, past experiences of physicians showing less concern about them, and little confidence that rural physicians had the needed expertise or would make an appropriate referral.

The study is just the first step in a series of efforts to improve melanoma outcomes in high-risk populations, which is being pursued through Stanford University’s Wipe Out Melanoma–California statewide initiative and research consortium. “What we aim to do is use this knowledge to now design programs to reach the populations who are more likely to present with worse disease, and to prevent that disease from happening. These qualitative analyses are few and far between in the world of melanoma, and we’re really happy to really push this envelope and change the way we deliver preventive and early detection efforts,” said Dr. Swetter, who is a professor of dermatology and director of the pigmented lesion/melanoma and cutaneous oncology programs at Stanford (Calif.) University Medical Center. Dr. Swetter also chairs the National Comprehensive Cancer Network guidelines for cutaneous melanoma.

The study could also improve care of advanced melanoma. “There’s clear evidence that many of these patient and SES factors, economic and knowledge barriers are the same when it comes to getting patients with advanced melanoma into appropriate care and on clinical trials, and that’s true across all races and ethnicities,” said Dr. Swetter.

The ultimate goal of these approaches is to give individuals greater “self-efficacy, such that a person feels more competent to manage his or her own health outcomes. One aspect of this approach is the use of novel technology such as smartphone apps that can track moles or help visualize lesions during teledermatology. “I think that the future of melanoma prevention and early detection is bright, especially if we incorporate novel technologies and engage patients and their communities in the effort. It’s a different strategy, as opposed to the top-down approach of physicians imparting knowledge and providing the exam. Increasing community engagement is critical to reaching the populations at highest risk for advanced disease and getting them into care and detection early,” Dr. Swetter said.

Dr. Swetter has no relevant financial disclosures.

TAMPA – Pre-exposure prophylaxis (PrEP) has shown to be effective in many clinical and real-world studies, but concerns remain, according to research presented at the annual meeting of the Association of Nurses in AIDS Care (ANAC).

Only about 20% of people who could benefit from PrEP use the preventative medication, for example. Another concern is adherence, as regular use generally drops off over time, rarely lasting more than a few months for most people.

Furthermore, most studies to date evaluated safety and effectiveness of PrEP options among men who have sex with men. Now the focus is increasing on other populations, including women at risk of HIV exposure.  

Researchers working on new forms and formulations of PrEP are looking for ways to address those challenges.

No matter the target population, new options are needed that fit more seamlessly into people’s sex lives, said Craig W. Hendrix, MD, professor and director of the Division of Clinical Pharmacology at Johns Hopkins University School of Medicine, Baltimore.

“What I hear a lot of folks say [is] there are two or three options for PrEP, so why do we need more? We need choices that fit into a broader range of lifestyles,” Dr. Hendrix said.

For example, a medically fortified douche containing PrEP might be more likely to be used by people who use a douche before or after sex on a regular basis. This is called a “behaviorally congruent” strategy, Dr. Hendrix said.

In addition to a medical douche, formulations designed to continuously deliver PrEP, such as a subdermal implant, are in the works as well.

Another option for women, the dapivirine vaginal ring, is available internationally but not in the United States. “It was withdrawn from [Food and Drug Administration] consideration by the sponsor. I think it’s a huge loss not to have that,” Dr. Hendrix said.

During development, “frequent expulsions forced reformulation to a less stiff ring,” Dr. Hendrix said. “I don’t imagine that’s terrific, but it shows how important it is to have something that fits the anatomy and the lifestyle.”

“Currently, we have in the U.S. three licensed, really terrific options for PrEP, and they’re all for men that have sex with men and transgender women,” Dr. Hendrix said.
 

Three current options

The three current PrEP regimens in the United States often go by their abbreviations: F/TDF, F/TAF, and CAB-IM.

• F/TDF is emtricitabine (F) 200 mg in combination with tenofovir disoproxil fumarate (TDF) 300 mg (Truvada, Gilead or generics)
• F/TAF is emtricitabine (F) 200 mg in combination with tenofovir alafenamide (TAF) 25 mg (Descovy, Gilead)
• CAB-IM is cabotegravir (CAB) 600 mg injection (Apretude, GlaxoSmithKline)

There is an important distinction: Daily oral PrEP with F/TDF is recommended to prevent HIV infection among all people at risk through sex or injection drug use. Daily oral PrEP with F/TAF is recommended to prevent HIV infection among people at risk through sex, excluding people at risk through receptive vaginal sex, the CDC notes.

The cost-effectiveness of the injection remains a potential issue, Dr. Hendrix said. On the other hand, “cost-effectiveness goes out the window if there is no adherence.”
 

An active pipeline

There are 24 new PrEP products in development, as well as 24 other multipurpose prevention technologies (MPTs), which are combination products containing PrEP and one or two other medications.

These 48 products include 28 unique antiviral and contraceptive drugs and 12 delivery methods or formulations. “Why so many?” Dr. Hendrix asked. “Many will not make it through development.”

Pills that include HIV PrEP and contraception or PrEP and sexually transmitted infection (STI) treatment are being evaluated, for example. “HIV risk, pregnancy risk, and other viral STIs overlap. Ideally, you can have one target for all three. That would increase efficiency of dosing and adherence,” Dr. Hendrix said.

Dual prevention pills (DPPs) hypothetically provide HIV PrEP and contraception better than either product alone, Dr. Hendrix said. Plans are to market them as family planning or women’s health products to avoid any stigma or distrust associated with HIV PrEP. An initial rollout is planned in 2024 in sub-Saharan Africa where the unmet need is highest, he added.

“Imagine how effective this could be in women in the United States,” Dr. Hendrix said. “My hope is fourth-quarter 2024” availability in the United States.

A way to prevent STIs and HIV in an all-in-one product “would be terrific,” Dr. Hendrix said.

“I think we’re going to see a lot more innovation going in that direction. The pill is close. The other things are going to be further off because the regulatory pathway is a little more complicated.”
 

Longer lasting protection?

All of the innovations have gone one of two directions, Dr. Hendrix said. One direction is to make PrEP even longer acting, “so that you have even less to worry [about] in terms of adherence.”

Going forward, “most of the focus has all been on continuously acting or long-active PrEP. It’s getting longer and longer: We’ve got 2 months, and they’re looking at a 6-month subcutaneous injection,” Dr. Hendrix said. The investigational agent lenacapavir is in development as PrEP, as well as for HIV treatment.

“This could get us from 2 to 6 months,” Dr. Hendrix said.

Some of the subcutaneous implants look as if they could provide PrEP for up to 12 months, he added. “An implant could also avoid peaks and troughs with bi-monthly injections.”
 

On-demand PrEP

The other direction is on-demand. “This is for the folks that don’t want drug in their body all the time. They only want it when they need it. And a twist on that ... is actually using products that are already used with sex now but medicating them.”

On-demand rectal options include a medicated douche and a fast-dissolving insert or suppository.

Fast-dissolving vaginal inserts are also in development. “These inserts are small, easy to store, inexpensive, and possibly inapparent to a partner,” Dr. Hendrix said.

Phase 2 studies will need to determine if these products “fit into folks’ active sex lives,” he said. “There’s still a need for human-friendly, human-designed products.”

A rectal microbicide that got as far as Phase 2 research provides a cautionary tale. The concentrations and the biology worked fine, Dr. Hendrix said. “It was a gel with an applicator, and it just was not liked by the folks in the study.” He added, “Your adherence is going to be in the tank if you’ve got a product that people don’t like to use.”
 

‘Extremely excited’

Asked for her perspective on Dr. Hendrix’s presentation, session moderator Rasheeta D. Chandler, PhD, RN, an associate professor at the Nell Hodgson Woodruff School of Nursing at Emory University, Atlanta, said: “I am extremely excited, because I work with cisgender women, particularly with underserved women and women of color, and there’s a tendency to focus on men who have sex with men.”

“I understand, because they are the population that is most affected, but Black women are also extremely affected by this disease,” Dr. Chandler told this news organization.

Dr. Chandler applauded Dr. Hendrix for addressing women’s health needs as well and not treating PrEP in women “as an afterthought.”

“Finally, our voices are being heard that [PrEP] should be equitable across all different types of individuals who identify differently in a sexual context,” Dr. Chandler said.

More work is warranted to evaluate PrEP in other populations, including transgender men and individuals who inject drugs, Dr. Hendrix said.

For more information and updates on HIV PrEP and MPTs, visit the website of the nonprofit AIDS Vaccine Advocacy Coalition.

Dr. Hendrix has disclosed receiving research grants from Gilead and Merck. Dr. Chandler has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TAMPA – Pre-exposure prophylaxis (PrEP) has shown to be effective in many clinical and real-world studies, but concerns remain, according to research presented at the annual meeting of the Association of Nurses in AIDS Care (ANAC).

Only about 20% of people who could benefit from PrEP use the preventative medication, for example. Another concern is adherence, as regular use generally drops off over time, rarely lasting more than a few months for most people.

Furthermore, most studies to date evaluated safety and effectiveness of PrEP options among men who have sex with men. Now the focus is increasing on other populations, including women at risk of HIV exposure.  

Researchers working on new forms and formulations of PrEP are looking for ways to address those challenges.

No matter the target population, new options are needed that fit more seamlessly into people’s sex lives, said Craig W. Hendrix, MD, professor and director of the Division of Clinical Pharmacology at Johns Hopkins University School of Medicine, Baltimore.

“What I hear a lot of folks say [is] there are two or three options for PrEP, so why do we need more? We need choices that fit into a broader range of lifestyles,” Dr. Hendrix said.

For example, a medically fortified douche containing PrEP might be more likely to be used by people who use a douche before or after sex on a regular basis. This is called a “behaviorally congruent” strategy, Dr. Hendrix said.

In addition to a medical douche, formulations designed to continuously deliver PrEP, such as a subdermal implant, are in the works as well.

Another option for women, the dapivirine vaginal ring, is available internationally but not in the United States. “It was withdrawn from [Food and Drug Administration] consideration by the sponsor. I think it’s a huge loss not to have that,” Dr. Hendrix said.

During development, “frequent expulsions forced reformulation to a less stiff ring,” Dr. Hendrix said. “I don’t imagine that’s terrific, but it shows how important it is to have something that fits the anatomy and the lifestyle.”

“Currently, we have in the U.S. three licensed, really terrific options for PrEP, and they’re all for men that have sex with men and transgender women,” Dr. Hendrix said.
 

Three current options

The three current PrEP regimens in the United States often go by their abbreviations: F/TDF, F/TAF, and CAB-IM.

• F/TDF is emtricitabine (F) 200 mg in combination with tenofovir disoproxil fumarate (TDF) 300 mg (Truvada, Gilead or generics)
• F/TAF is emtricitabine (F) 200 mg in combination with tenofovir alafenamide (TAF) 25 mg (Descovy, Gilead)
• CAB-IM is cabotegravir (CAB) 600 mg injection (Apretude, GlaxoSmithKline)

There is an important distinction: Daily oral PrEP with F/TDF is recommended to prevent HIV infection among all people at risk through sex or injection drug use. Daily oral PrEP with F/TAF is recommended to prevent HIV infection among people at risk through sex, excluding people at risk through receptive vaginal sex, the CDC notes.

The cost-effectiveness of the injection remains a potential issue, Dr. Hendrix said. On the other hand, “cost-effectiveness goes out the window if there is no adherence.”
 

An active pipeline

There are 24 new PrEP products in development, as well as 24 other multipurpose prevention technologies (MPTs), which are combination products containing PrEP and one or two other medications.

These 48 products include 28 unique antiviral and contraceptive drugs and 12 delivery methods or formulations. “Why so many?” Dr. Hendrix asked. “Many will not make it through development.”

Pills that include HIV PrEP and contraception or PrEP and sexually transmitted infection (STI) treatment are being evaluated, for example. “HIV risk, pregnancy risk, and other viral STIs overlap. Ideally, you can have one target for all three. That would increase efficiency of dosing and adherence,” Dr. Hendrix said.

Dual prevention pills (DPPs) hypothetically provide HIV PrEP and contraception better than either product alone, Dr. Hendrix said. Plans are to market them as family planning or women’s health products to avoid any stigma or distrust associated with HIV PrEP. An initial rollout is planned in 2024 in sub-Saharan Africa where the unmet need is highest, he added.

“Imagine how effective this could be in women in the United States,” Dr. Hendrix said. “My hope is fourth-quarter 2024” availability in the United States.

A way to prevent STIs and HIV in an all-in-one product “would be terrific,” Dr. Hendrix said.

“I think we’re going to see a lot more innovation going in that direction. The pill is close. The other things are going to be further off because the regulatory pathway is a little more complicated.”
 

Longer lasting protection?

All of the innovations have gone one of two directions, Dr. Hendrix said. One direction is to make PrEP even longer acting, “so that you have even less to worry [about] in terms of adherence.”

Going forward, “most of the focus has all been on continuously acting or long-active PrEP. It’s getting longer and longer: We’ve got 2 months, and they’re looking at a 6-month subcutaneous injection,” Dr. Hendrix said. The investigational agent lenacapavir is in development as PrEP, as well as for HIV treatment.

“This could get us from 2 to 6 months,” Dr. Hendrix said.

Some of the subcutaneous implants look as if they could provide PrEP for up to 12 months, he added. “An implant could also avoid peaks and troughs with bi-monthly injections.”
 

On-demand PrEP

The other direction is on-demand. “This is for the folks that don’t want drug in their body all the time. They only want it when they need it. And a twist on that ... is actually using products that are already used with sex now but medicating them.”

On-demand rectal options include a medicated douche and a fast-dissolving insert or suppository.

Fast-dissolving vaginal inserts are also in development. “These inserts are small, easy to store, inexpensive, and possibly inapparent to a partner,” Dr. Hendrix said.

Phase 2 studies will need to determine if these products “fit into folks’ active sex lives,” he said. “There’s still a need for human-friendly, human-designed products.”

A rectal microbicide that got as far as Phase 2 research provides a cautionary tale. The concentrations and the biology worked fine, Dr. Hendrix said. “It was a gel with an applicator, and it just was not liked by the folks in the study.” He added, “Your adherence is going to be in the tank if you’ve got a product that people don’t like to use.”
 

‘Extremely excited’

Asked for her perspective on Dr. Hendrix’s presentation, session moderator Rasheeta D. Chandler, PhD, RN, an associate professor at the Nell Hodgson Woodruff School of Nursing at Emory University, Atlanta, said: “I am extremely excited, because I work with cisgender women, particularly with underserved women and women of color, and there’s a tendency to focus on men who have sex with men.”

“I understand, because they are the population that is most affected, but Black women are also extremely affected by this disease,” Dr. Chandler told this news organization.

Dr. Chandler applauded Dr. Hendrix for addressing women’s health needs as well and not treating PrEP in women “as an afterthought.”

“Finally, our voices are being heard that [PrEP] should be equitable across all different types of individuals who identify differently in a sexual context,” Dr. Chandler said.

More work is warranted to evaluate PrEP in other populations, including transgender men and individuals who inject drugs, Dr. Hendrix said.

For more information and updates on HIV PrEP and MPTs, visit the website of the nonprofit AIDS Vaccine Advocacy Coalition.

Dr. Hendrix has disclosed receiving research grants from Gilead and Merck. Dr. Chandler has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TAMPA – Pre-exposure prophylaxis (PrEP) has shown to be effective in many clinical and real-world studies, but concerns remain, according to research presented at the annual meeting of the Association of Nurses in AIDS Care (ANAC).

Only about 20% of people who could benefit from PrEP use the preventative medication, for example. Another concern is adherence, as regular use generally drops off over time, rarely lasting more than a few months for most people.

Furthermore, most studies to date evaluated safety and effectiveness of PrEP options among men who have sex with men. Now the focus is increasing on other populations, including women at risk of HIV exposure.  

Researchers working on new forms and formulations of PrEP are looking for ways to address those challenges.

No matter the target population, new options are needed that fit more seamlessly into people’s sex lives, said Craig W. Hendrix, MD, professor and director of the Division of Clinical Pharmacology at Johns Hopkins University School of Medicine, Baltimore.

“What I hear a lot of folks say [is] there are two or three options for PrEP, so why do we need more? We need choices that fit into a broader range of lifestyles,” Dr. Hendrix said.

For example, a medically fortified douche containing PrEP might be more likely to be used by people who use a douche before or after sex on a regular basis. This is called a “behaviorally congruent” strategy, Dr. Hendrix said.

In addition to a medical douche, formulations designed to continuously deliver PrEP, such as a subdermal implant, are in the works as well.

Another option for women, the dapivirine vaginal ring, is available internationally but not in the United States. “It was withdrawn from [Food and Drug Administration] consideration by the sponsor. I think it’s a huge loss not to have that,” Dr. Hendrix said.

During development, “frequent expulsions forced reformulation to a less stiff ring,” Dr. Hendrix said. “I don’t imagine that’s terrific, but it shows how important it is to have something that fits the anatomy and the lifestyle.”

“Currently, we have in the U.S. three licensed, really terrific options for PrEP, and they’re all for men that have sex with men and transgender women,” Dr. Hendrix said.
 

Three current options

The three current PrEP regimens in the United States often go by their abbreviations: F/TDF, F/TAF, and CAB-IM.

• F/TDF is emtricitabine (F) 200 mg in combination with tenofovir disoproxil fumarate (TDF) 300 mg (Truvada, Gilead or generics)
• F/TAF is emtricitabine (F) 200 mg in combination with tenofovir alafenamide (TAF) 25 mg (Descovy, Gilead)
• CAB-IM is cabotegravir (CAB) 600 mg injection (Apretude, GlaxoSmithKline)

There is an important distinction: Daily oral PrEP with F/TDF is recommended to prevent HIV infection among all people at risk through sex or injection drug use. Daily oral PrEP with F/TAF is recommended to prevent HIV infection among people at risk through sex, excluding people at risk through receptive vaginal sex, the CDC notes.

The cost-effectiveness of the injection remains a potential issue, Dr. Hendrix said. On the other hand, “cost-effectiveness goes out the window if there is no adherence.”
 

An active pipeline

There are 24 new PrEP products in development, as well as 24 other multipurpose prevention technologies (MPTs), which are combination products containing PrEP and one or two other medications.

These 48 products include 28 unique antiviral and contraceptive drugs and 12 delivery methods or formulations. “Why so many?” Dr. Hendrix asked. “Many will not make it through development.”

Pills that include HIV PrEP and contraception or PrEP and sexually transmitted infection (STI) treatment are being evaluated, for example. “HIV risk, pregnancy risk, and other viral STIs overlap. Ideally, you can have one target for all three. That would increase efficiency of dosing and adherence,” Dr. Hendrix said.

Dual prevention pills (DPPs) hypothetically provide HIV PrEP and contraception better than either product alone, Dr. Hendrix said. Plans are to market them as family planning or women’s health products to avoid any stigma or distrust associated with HIV PrEP. An initial rollout is planned in 2024 in sub-Saharan Africa where the unmet need is highest, he added.

“Imagine how effective this could be in women in the United States,” Dr. Hendrix said. “My hope is fourth-quarter 2024” availability in the United States.

A way to prevent STIs and HIV in an all-in-one product “would be terrific,” Dr. Hendrix said.

“I think we’re going to see a lot more innovation going in that direction. The pill is close. The other things are going to be further off because the regulatory pathway is a little more complicated.”
 

Longer lasting protection?

All of the innovations have gone one of two directions, Dr. Hendrix said. One direction is to make PrEP even longer acting, “so that you have even less to worry [about] in terms of adherence.”

Going forward, “most of the focus has all been on continuously acting or long-active PrEP. It’s getting longer and longer: We’ve got 2 months, and they’re looking at a 6-month subcutaneous injection,” Dr. Hendrix said. The investigational agent lenacapavir is in development as PrEP, as well as for HIV treatment.

“This could get us from 2 to 6 months,” Dr. Hendrix said.

Some of the subcutaneous implants look as if they could provide PrEP for up to 12 months, he added. “An implant could also avoid peaks and troughs with bi-monthly injections.”
 

On-demand PrEP

The other direction is on-demand. “This is for the folks that don’t want drug in their body all the time. They only want it when they need it. And a twist on that ... is actually using products that are already used with sex now but medicating them.”

On-demand rectal options include a medicated douche and a fast-dissolving insert or suppository.

Fast-dissolving vaginal inserts are also in development. “These inserts are small, easy to store, inexpensive, and possibly inapparent to a partner,” Dr. Hendrix said.

Phase 2 studies will need to determine if these products “fit into folks’ active sex lives,” he said. “There’s still a need for human-friendly, human-designed products.”

A rectal microbicide that got as far as Phase 2 research provides a cautionary tale. The concentrations and the biology worked fine, Dr. Hendrix said. “It was a gel with an applicator, and it just was not liked by the folks in the study.” He added, “Your adherence is going to be in the tank if you’ve got a product that people don’t like to use.”
 

‘Extremely excited’

Asked for her perspective on Dr. Hendrix’s presentation, session moderator Rasheeta D. Chandler, PhD, RN, an associate professor at the Nell Hodgson Woodruff School of Nursing at Emory University, Atlanta, said: “I am extremely excited, because I work with cisgender women, particularly with underserved women and women of color, and there’s a tendency to focus on men who have sex with men.”

“I understand, because they are the population that is most affected, but Black women are also extremely affected by this disease,” Dr. Chandler told this news organization.

Dr. Chandler applauded Dr. Hendrix for addressing women’s health needs as well and not treating PrEP in women “as an afterthought.”

“Finally, our voices are being heard that [PrEP] should be equitable across all different types of individuals who identify differently in a sexual context,” Dr. Chandler said.

More work is warranted to evaluate PrEP in other populations, including transgender men and individuals who inject drugs, Dr. Hendrix said.

For more information and updates on HIV PrEP and MPTs, visit the website of the nonprofit AIDS Vaccine Advocacy Coalition.

Dr. Hendrix has disclosed receiving research grants from Gilead and Merck. Dr. Chandler has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TAMPA – People living with HIV (PLWH) were more likely than other populations to get vaccinated for flu and COVID-19, to seek reputable sources of information, and to be connected through essential community organizations that share essential health and wellness information, according to the results of a large survey.

PLWH, therefore, would have been an ideal model population for creating and disseminating effective messaging around COVID-19 immunizations earlier in the pandemic, said Kathleen Gallagher, MPH, an epidemiologist, researcher, and health services administrator at the Patient Advocate Foundation.

The PLWH community can still offer valuable insights into effective ways to reach out to people, to disseminate correct information, and to link people with resources, Ms. Gallagher said during a poster presentation at the annual meeting of the Association of Nurses in AIDS Care (ANAC).

In addition, the PLWH response to the pandemic illustrates the importance of community. Local, community-based organizations “are the people that these individuals trust, they are people entrenched in their community, and they have existing relationships with them in terms of getting vaccinated and listening to their concerns,” Ms. Gallagher said.

“It’s a missed opportunity.”
 

A highly compliant group

The July 2021 survey of 271 PLWH was part of a larger, longitudinal survey of 1,400 people with any chronic illness asked about attitudes and barriers to vaccination. The PLWH population was important to focus on, the researchers note, because they could be potentially high risk for more serious COVID-19 outcomes.

The PLWH group was 81% White and 90% male, and 83% were age 56 or older. In addition, 86% had an annual household income below $48,000.

Ninety-three percent of the PLWH group had had flu vaccination in the prior 3 years and received at least one COVID-19 vaccination.
 

Unable vs. unwilling to vaccinate

Ms. Gallagher and colleagues found 12 people (4%) in the PLWH group did not get vaccinated against COVID-19. It’s a small number, “so you have to take this with a grain of salt,” she said. “But we asked them why they were hesitant. They either were unable or unwilling – and the unable part is not surprising.”

Those who were unable to get vaccinated were either homebound or had concerns about being in a clinic where they could be exposed to COVID while waiting to get the vaccine.

“And then there were some who were just not willing” to get vaccinated, Ms. Gallagher said. She added most cited vaccine safety concerns and “a lot of the misinformation or confusing information around efficacy.”
 

Trusted information sources

Although people reported getting COVID-19 vaccine information from multiple sources, including online and from television, 64% or nearly two-thirds sought information from their doctors or health care teams.

In fact, doctors emerged as the most trusted source, as indicated by 72% of PLWH.

“I was a little surprised that doctors scored so highly because, sometimes in other cohorts that we looked at, it wasn’t the case,” Ms. Gallagher said. However, she added, a lot of PLWH “have a very strong trust bond with their provider because this is a very personal, very sensitive diagnosis.”

How did social media score? “A whopping 1%,” she said. “So at least this was a savvy group, and they realized that that was not the place to go for vaccination information.”
 

Overcoming barriers

A lack of vaccine availability at the time of their appointment was the number one barrier to immunization. Also, a small number of people said knowing someone who had an adverse reaction to COVID-19 vaccination was a barrier for them. Ms. Gallagher explained that, by definition in the survey, an adverse reaction to vaccination had to be serious enough to drive people to seek medical care.

When asked to comment on the poster, Andrew Komensky, RN, told this news organization that he found the results “interesting, because I’m an infection preventionist, in addition to being an HIV nurse.” He is director of infection prevention and control at CharterCARE Health Partners, Providence, R.I.

Mr. Komensky said he was surprised that a high proportion of PLWH cited their doctor – and not their nurse – as the most trusted source of information. “In my experience in COVID care ... it was a nursing staff who had most of the contact with patients, who did most of the education, and provided most of the information surrounding vaccination and potential side effects.”

It made sense to Mr. Komensky that the PLWH population would be compliant with vaccinations. “People who are living with HIV do everything they possibly can just to stay healthy.”

A version of this article first appeared on Medscape.com.

TAMPA – People living with HIV (PLWH) were more likely than other populations to get vaccinated for flu and COVID-19, to seek reputable sources of information, and to be connected through essential community organizations that share essential health and wellness information, according to the results of a large survey.

PLWH, therefore, would have been an ideal model population for creating and disseminating effective messaging around COVID-19 immunizations earlier in the pandemic, said Kathleen Gallagher, MPH, an epidemiologist, researcher, and health services administrator at the Patient Advocate Foundation.

The PLWH community can still offer valuable insights into effective ways to reach out to people, to disseminate correct information, and to link people with resources, Ms. Gallagher said during a poster presentation at the annual meeting of the Association of Nurses in AIDS Care (ANAC).

In addition, the PLWH response to the pandemic illustrates the importance of community. Local, community-based organizations “are the people that these individuals trust, they are people entrenched in their community, and they have existing relationships with them in terms of getting vaccinated and listening to their concerns,” Ms. Gallagher said.

“It’s a missed opportunity.”
 

A highly compliant group

The July 2021 survey of 271 PLWH was part of a larger, longitudinal survey of 1,400 people with any chronic illness asked about attitudes and barriers to vaccination. The PLWH population was important to focus on, the researchers note, because they could be potentially high risk for more serious COVID-19 outcomes.

The PLWH group was 81% White and 90% male, and 83% were age 56 or older. In addition, 86% had an annual household income below $48,000.

Ninety-three percent of the PLWH group had had flu vaccination in the prior 3 years and received at least one COVID-19 vaccination.
 

Unable vs. unwilling to vaccinate

Ms. Gallagher and colleagues found 12 people (4%) in the PLWH group did not get vaccinated against COVID-19. It’s a small number, “so you have to take this with a grain of salt,” she said. “But we asked them why they were hesitant. They either were unable or unwilling – and the unable part is not surprising.”

Those who were unable to get vaccinated were either homebound or had concerns about being in a clinic where they could be exposed to COVID while waiting to get the vaccine.

“And then there were some who were just not willing” to get vaccinated, Ms. Gallagher said. She added most cited vaccine safety concerns and “a lot of the misinformation or confusing information around efficacy.”
 

Trusted information sources

Although people reported getting COVID-19 vaccine information from multiple sources, including online and from television, 64% or nearly two-thirds sought information from their doctors or health care teams.

In fact, doctors emerged as the most trusted source, as indicated by 72% of PLWH.

“I was a little surprised that doctors scored so highly because, sometimes in other cohorts that we looked at, it wasn’t the case,” Ms. Gallagher said. However, she added, a lot of PLWH “have a very strong trust bond with their provider because this is a very personal, very sensitive diagnosis.”

How did social media score? “A whopping 1%,” she said. “So at least this was a savvy group, and they realized that that was not the place to go for vaccination information.”
 

Overcoming barriers

A lack of vaccine availability at the time of their appointment was the number one barrier to immunization. Also, a small number of people said knowing someone who had an adverse reaction to COVID-19 vaccination was a barrier for them. Ms. Gallagher explained that, by definition in the survey, an adverse reaction to vaccination had to be serious enough to drive people to seek medical care.

When asked to comment on the poster, Andrew Komensky, RN, told this news organization that he found the results “interesting, because I’m an infection preventionist, in addition to being an HIV nurse.” He is director of infection prevention and control at CharterCARE Health Partners, Providence, R.I.

Mr. Komensky said he was surprised that a high proportion of PLWH cited their doctor – and not their nurse – as the most trusted source of information. “In my experience in COVID care ... it was a nursing staff who had most of the contact with patients, who did most of the education, and provided most of the information surrounding vaccination and potential side effects.”

It made sense to Mr. Komensky that the PLWH population would be compliant with vaccinations. “People who are living with HIV do everything they possibly can just to stay healthy.”

A version of this article first appeared on Medscape.com.

TAMPA – People living with HIV (PLWH) were more likely than other populations to get vaccinated for flu and COVID-19, to seek reputable sources of information, and to be connected through essential community organizations that share essential health and wellness information, according to the results of a large survey.

PLWH, therefore, would have been an ideal model population for creating and disseminating effective messaging around COVID-19 immunizations earlier in the pandemic, said Kathleen Gallagher, MPH, an epidemiologist, researcher, and health services administrator at the Patient Advocate Foundation.

The PLWH community can still offer valuable insights into effective ways to reach out to people, to disseminate correct information, and to link people with resources, Ms. Gallagher said during a poster presentation at the annual meeting of the Association of Nurses in AIDS Care (ANAC).

In addition, the PLWH response to the pandemic illustrates the importance of community. Local, community-based organizations “are the people that these individuals trust, they are people entrenched in their community, and they have existing relationships with them in terms of getting vaccinated and listening to their concerns,” Ms. Gallagher said.

“It’s a missed opportunity.”
 

A highly compliant group

The July 2021 survey of 271 PLWH was part of a larger, longitudinal survey of 1,400 people with any chronic illness asked about attitudes and barriers to vaccination. The PLWH population was important to focus on, the researchers note, because they could be potentially high risk for more serious COVID-19 outcomes.

The PLWH group was 81% White and 90% male, and 83% were age 56 or older. In addition, 86% had an annual household income below $48,000.

Ninety-three percent of the PLWH group had had flu vaccination in the prior 3 years and received at least one COVID-19 vaccination.
 

Unable vs. unwilling to vaccinate

Ms. Gallagher and colleagues found 12 people (4%) in the PLWH group did not get vaccinated against COVID-19. It’s a small number, “so you have to take this with a grain of salt,” she said. “But we asked them why they were hesitant. They either were unable or unwilling – and the unable part is not surprising.”

Those who were unable to get vaccinated were either homebound or had concerns about being in a clinic where they could be exposed to COVID while waiting to get the vaccine.

“And then there were some who were just not willing” to get vaccinated, Ms. Gallagher said. She added most cited vaccine safety concerns and “a lot of the misinformation or confusing information around efficacy.”
 

Trusted information sources

Although people reported getting COVID-19 vaccine information from multiple sources, including online and from television, 64% or nearly two-thirds sought information from their doctors or health care teams.

In fact, doctors emerged as the most trusted source, as indicated by 72% of PLWH.

“I was a little surprised that doctors scored so highly because, sometimes in other cohorts that we looked at, it wasn’t the case,” Ms. Gallagher said. However, she added, a lot of PLWH “have a very strong trust bond with their provider because this is a very personal, very sensitive diagnosis.”

How did social media score? “A whopping 1%,” she said. “So at least this was a savvy group, and they realized that that was not the place to go for vaccination information.”
 

Overcoming barriers

A lack of vaccine availability at the time of their appointment was the number one barrier to immunization. Also, a small number of people said knowing someone who had an adverse reaction to COVID-19 vaccination was a barrier for them. Ms. Gallagher explained that, by definition in the survey, an adverse reaction to vaccination had to be serious enough to drive people to seek medical care.

When asked to comment on the poster, Andrew Komensky, RN, told this news organization that he found the results “interesting, because I’m an infection preventionist, in addition to being an HIV nurse.” He is director of infection prevention and control at CharterCARE Health Partners, Providence, R.I.

Mr. Komensky said he was surprised that a high proportion of PLWH cited their doctor – and not their nurse – as the most trusted source of information. “In my experience in COVID care ... it was a nursing staff who had most of the contact with patients, who did most of the education, and provided most of the information surrounding vaccination and potential side effects.”

It made sense to Mr. Komensky that the PLWH population would be compliant with vaccinations. “People who are living with HIV do everything they possibly can just to stay healthy.”

A version of this article first appeared on Medscape.com.