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Sequential chemoradiation improves DFS in early-stage cervical cancer
In the study’s intent-to-treat (ITT) population, the 3-year DFS rate was significantly higher among patients who received sequential chemoradiation than among patients who received concurrent chemoradiation or radiation alone.
“After an adjustment for baseline presence of lymph node metastasis, we found that sequential chemoradiation decreased, by 40% to 50%, the recurrence risk, compared with the other two groups,” said investigator He Huang, MD, of Sun Yat-Sen University Cancer Center in Guangzhou, China.
Dr. Huang presented these findings as part of the American Society of Clinical Oncology virtual scientific program.
Study rationale and details
“As we know, early-stage cervical cancer can be cured after treatment,” Dr. Huang said. “However, the risk of recurrence remains higher among patients with high-risk factors, including lymph node metastases, positive surgical margins, and parametrial invasion. Postoperative adjuvant radiation and chemotherapy may result in favorable survival for patients with high-risk factors.”
Although the efficacy of concurrent radiation with single-agent cisplatin has been demonstrated in primary treatment for local advanced cervical cancer, it has not been assessed as adjuvant treatment for early-stage cervical cancer in a randomized, controlled trial, Dr. Huang explained.
“Another question is whether patients with intermediate-risk factors could benefit from the concurrent chemotherapy [with] radiation,” he said. “So far, we don’t have enough evidence.”
To gain some insight, Dr. Huang and colleagues initiated the STARS trial. The trial enrolled patients with stage IB1-IIA2 cervical cancer and at least one adverse risk factor after radical hysterectomy. Patients had a median age of 48 years, and most had stage IB1 or IIA1 disease.
The patients were randomized 1:1:1 to receive radiation alone, concurrent chemoradiation, or sequential chemoradiation.
All patients received pelvic radiation at 45-50 Gy. Patients in the concurrent chemoradiation arm also received five doses of weekly cisplatin at 30-40 mg/m2.
Patients in the sequential chemoradiation arm received 60-75 mg/m2 of weekly cisplatin plus 135-175 mg/m2 of paclitaxel in 21-day cycles, with two cycles given before and two cycles given after radiotherapy.
The treatment groups were comparable with respect to histologic subtypes, lymphovascular invasion rates, parametrial or surgical margin involvement, deep stromal involvement, tumor grade, minimally invasive surgery rates, and neoadjuvant chemotherapy, Dr. Huang said. He added, however, that lymph node metastasis was lowest in the radiation-only arm.
DFS results
In the ITT population, patients who received sequential chemoradiation had significantly better DFS compared with patients in the other treatment arms. The ITT population included 353 patients in the sequential chemoradiation arm, 345 patients in the concurrent chemoradiation arm, and 350 patients in the radiation-only arm.
The 3-year DFS rates were 90% in patients randomized to sequential chemoradiation, 85% in patients randomized to concurrent chemoradiation, and 82% in patients randomized to radiation alone (hazard ratios, 0.52 for sequential chemoradiation vs. radiation alone and 0.65 for sequential vs. concurrent chemoradiation; P = .03).
Subgroup analyses showed a DFS benefit with sequential chemoradiation versus radiation alone across histology types, tumor grades, and tumor size, Dr. Huang noted.
In the per-protocol population, sequential chemoradiation was associated with better DFS when compared with radiation alone. However, there were no significant differences between the sequential and concurrent chemoradiation arms or the concurrent chemoradiation and radiation-only arms.
The per-protocol population included 235 patients in the sequential chemoradiation arm, 190 patients in the concurrent chemoradiation arm, and 324 patients in the radiation-only arm.
In the per-protocol population, the 3-year DFS rates were 91% in patients randomized to sequential chemoradiation, 86% in patients randomized to concurrent chemoradiation, and 82% in patients randomized to radiation alone (HRs, 0.47 for sequential vs. radiation alone and 0.67 for sequential vs. concurrent; P = .026).
In the overall population, DFS was superior among patients with intermediate-risk versus high-risk factors. The 3-year DFS rates were 90% and 74%, respectively (P < .05).
Overall survival and safety
As for overall survival (OS), sequential chemoradiation showed a trend toward improvement at 5 years, compared with the other treatment groups. However, the differences were not statistically significant in either the ITT or per-protocol populations.
In the ITT population, the 5-year OS was 92% in the sequential chemoradiation arm, 89% in the concurrent chemoradiation arm, and 88% in the radiation-only arm. In the per-protocol population, the 5-year OS rates were 93%, 90%, and 88%, respectively.
Patients with intermediate-risk factors had a more favorable OS. The 5-year OS rate was 93% in patients with intermediate-risk factors and 81% in patients with high-risk factors (P < .05).
Dr. Huang noted that patients in the radiation-only arm experienced fewer grade 3-4 adverse events than the other patients. Less neutropenia, nausea, and vomiting were observed in the radiation-only arm.
There was more grade 3-4 nausea and vomiting in the concurrent chemoradiation arm than in the sequential chemoradiation arm.
However, Dr. Huang noted that “adding chemotherapy to radiation did not impact the patients’ quality of life in the long-term compared with radiation alone.
“In this study, sequential chemoradiation resulted in a better disease-free survival and a lower risk of cancer death for cervical cancer patients with adverse pathological factors,” he said. “We believe that sequential chemoradiation could be an optimal option for post-operative adjuvant treatment.”
This study was sponsored by Sun Yat-sen University in collaboration with Guangdong Provincial People’s Hospital, First Affiliated Hospital/Sun Yat-Sen University, Shenzhen People’s Hospital, and Cancer Hospital of Guangxi Medical University. Dr. Huang reported receiving honoraria, travel, accommodations, and expenses from AstraZeneca.
SOURCE: Huang H et al. ASCO 2020, Abstract 6007.
In the study’s intent-to-treat (ITT) population, the 3-year DFS rate was significantly higher among patients who received sequential chemoradiation than among patients who received concurrent chemoradiation or radiation alone.
“After an adjustment for baseline presence of lymph node metastasis, we found that sequential chemoradiation decreased, by 40% to 50%, the recurrence risk, compared with the other two groups,” said investigator He Huang, MD, of Sun Yat-Sen University Cancer Center in Guangzhou, China.
Dr. Huang presented these findings as part of the American Society of Clinical Oncology virtual scientific program.
Study rationale and details
“As we know, early-stage cervical cancer can be cured after treatment,” Dr. Huang said. “However, the risk of recurrence remains higher among patients with high-risk factors, including lymph node metastases, positive surgical margins, and parametrial invasion. Postoperative adjuvant radiation and chemotherapy may result in favorable survival for patients with high-risk factors.”
Although the efficacy of concurrent radiation with single-agent cisplatin has been demonstrated in primary treatment for local advanced cervical cancer, it has not been assessed as adjuvant treatment for early-stage cervical cancer in a randomized, controlled trial, Dr. Huang explained.
“Another question is whether patients with intermediate-risk factors could benefit from the concurrent chemotherapy [with] radiation,” he said. “So far, we don’t have enough evidence.”
To gain some insight, Dr. Huang and colleagues initiated the STARS trial. The trial enrolled patients with stage IB1-IIA2 cervical cancer and at least one adverse risk factor after radical hysterectomy. Patients had a median age of 48 years, and most had stage IB1 or IIA1 disease.
The patients were randomized 1:1:1 to receive radiation alone, concurrent chemoradiation, or sequential chemoradiation.
All patients received pelvic radiation at 45-50 Gy. Patients in the concurrent chemoradiation arm also received five doses of weekly cisplatin at 30-40 mg/m2.
Patients in the sequential chemoradiation arm received 60-75 mg/m2 of weekly cisplatin plus 135-175 mg/m2 of paclitaxel in 21-day cycles, with two cycles given before and two cycles given after radiotherapy.
The treatment groups were comparable with respect to histologic subtypes, lymphovascular invasion rates, parametrial or surgical margin involvement, deep stromal involvement, tumor grade, minimally invasive surgery rates, and neoadjuvant chemotherapy, Dr. Huang said. He added, however, that lymph node metastasis was lowest in the radiation-only arm.
DFS results
In the ITT population, patients who received sequential chemoradiation had significantly better DFS compared with patients in the other treatment arms. The ITT population included 353 patients in the sequential chemoradiation arm, 345 patients in the concurrent chemoradiation arm, and 350 patients in the radiation-only arm.
The 3-year DFS rates were 90% in patients randomized to sequential chemoradiation, 85% in patients randomized to concurrent chemoradiation, and 82% in patients randomized to radiation alone (hazard ratios, 0.52 for sequential chemoradiation vs. radiation alone and 0.65 for sequential vs. concurrent chemoradiation; P = .03).
Subgroup analyses showed a DFS benefit with sequential chemoradiation versus radiation alone across histology types, tumor grades, and tumor size, Dr. Huang noted.
In the per-protocol population, sequential chemoradiation was associated with better DFS when compared with radiation alone. However, there were no significant differences between the sequential and concurrent chemoradiation arms or the concurrent chemoradiation and radiation-only arms.
The per-protocol population included 235 patients in the sequential chemoradiation arm, 190 patients in the concurrent chemoradiation arm, and 324 patients in the radiation-only arm.
In the per-protocol population, the 3-year DFS rates were 91% in patients randomized to sequential chemoradiation, 86% in patients randomized to concurrent chemoradiation, and 82% in patients randomized to radiation alone (HRs, 0.47 for sequential vs. radiation alone and 0.67 for sequential vs. concurrent; P = .026).
In the overall population, DFS was superior among patients with intermediate-risk versus high-risk factors. The 3-year DFS rates were 90% and 74%, respectively (P < .05).
Overall survival and safety
As for overall survival (OS), sequential chemoradiation showed a trend toward improvement at 5 years, compared with the other treatment groups. However, the differences were not statistically significant in either the ITT or per-protocol populations.
In the ITT population, the 5-year OS was 92% in the sequential chemoradiation arm, 89% in the concurrent chemoradiation arm, and 88% in the radiation-only arm. In the per-protocol population, the 5-year OS rates were 93%, 90%, and 88%, respectively.
Patients with intermediate-risk factors had a more favorable OS. The 5-year OS rate was 93% in patients with intermediate-risk factors and 81% in patients with high-risk factors (P < .05).
Dr. Huang noted that patients in the radiation-only arm experienced fewer grade 3-4 adverse events than the other patients. Less neutropenia, nausea, and vomiting were observed in the radiation-only arm.
There was more grade 3-4 nausea and vomiting in the concurrent chemoradiation arm than in the sequential chemoradiation arm.
However, Dr. Huang noted that “adding chemotherapy to radiation did not impact the patients’ quality of life in the long-term compared with radiation alone.
“In this study, sequential chemoradiation resulted in a better disease-free survival and a lower risk of cancer death for cervical cancer patients with adverse pathological factors,” he said. “We believe that sequential chemoradiation could be an optimal option for post-operative adjuvant treatment.”
This study was sponsored by Sun Yat-sen University in collaboration with Guangdong Provincial People’s Hospital, First Affiliated Hospital/Sun Yat-Sen University, Shenzhen People’s Hospital, and Cancer Hospital of Guangxi Medical University. Dr. Huang reported receiving honoraria, travel, accommodations, and expenses from AstraZeneca.
SOURCE: Huang H et al. ASCO 2020, Abstract 6007.
In the study’s intent-to-treat (ITT) population, the 3-year DFS rate was significantly higher among patients who received sequential chemoradiation than among patients who received concurrent chemoradiation or radiation alone.
“After an adjustment for baseline presence of lymph node metastasis, we found that sequential chemoradiation decreased, by 40% to 50%, the recurrence risk, compared with the other two groups,” said investigator He Huang, MD, of Sun Yat-Sen University Cancer Center in Guangzhou, China.
Dr. Huang presented these findings as part of the American Society of Clinical Oncology virtual scientific program.
Study rationale and details
“As we know, early-stage cervical cancer can be cured after treatment,” Dr. Huang said. “However, the risk of recurrence remains higher among patients with high-risk factors, including lymph node metastases, positive surgical margins, and parametrial invasion. Postoperative adjuvant radiation and chemotherapy may result in favorable survival for patients with high-risk factors.”
Although the efficacy of concurrent radiation with single-agent cisplatin has been demonstrated in primary treatment for local advanced cervical cancer, it has not been assessed as adjuvant treatment for early-stage cervical cancer in a randomized, controlled trial, Dr. Huang explained.
“Another question is whether patients with intermediate-risk factors could benefit from the concurrent chemotherapy [with] radiation,” he said. “So far, we don’t have enough evidence.”
To gain some insight, Dr. Huang and colleagues initiated the STARS trial. The trial enrolled patients with stage IB1-IIA2 cervical cancer and at least one adverse risk factor after radical hysterectomy. Patients had a median age of 48 years, and most had stage IB1 or IIA1 disease.
The patients were randomized 1:1:1 to receive radiation alone, concurrent chemoradiation, or sequential chemoradiation.
All patients received pelvic radiation at 45-50 Gy. Patients in the concurrent chemoradiation arm also received five doses of weekly cisplatin at 30-40 mg/m2.
Patients in the sequential chemoradiation arm received 60-75 mg/m2 of weekly cisplatin plus 135-175 mg/m2 of paclitaxel in 21-day cycles, with two cycles given before and two cycles given after radiotherapy.
The treatment groups were comparable with respect to histologic subtypes, lymphovascular invasion rates, parametrial or surgical margin involvement, deep stromal involvement, tumor grade, minimally invasive surgery rates, and neoadjuvant chemotherapy, Dr. Huang said. He added, however, that lymph node metastasis was lowest in the radiation-only arm.
DFS results
In the ITT population, patients who received sequential chemoradiation had significantly better DFS compared with patients in the other treatment arms. The ITT population included 353 patients in the sequential chemoradiation arm, 345 patients in the concurrent chemoradiation arm, and 350 patients in the radiation-only arm.
The 3-year DFS rates were 90% in patients randomized to sequential chemoradiation, 85% in patients randomized to concurrent chemoradiation, and 82% in patients randomized to radiation alone (hazard ratios, 0.52 for sequential chemoradiation vs. radiation alone and 0.65 for sequential vs. concurrent chemoradiation; P = .03).
Subgroup analyses showed a DFS benefit with sequential chemoradiation versus radiation alone across histology types, tumor grades, and tumor size, Dr. Huang noted.
In the per-protocol population, sequential chemoradiation was associated with better DFS when compared with radiation alone. However, there were no significant differences between the sequential and concurrent chemoradiation arms or the concurrent chemoradiation and radiation-only arms.
The per-protocol population included 235 patients in the sequential chemoradiation arm, 190 patients in the concurrent chemoradiation arm, and 324 patients in the radiation-only arm.
In the per-protocol population, the 3-year DFS rates were 91% in patients randomized to sequential chemoradiation, 86% in patients randomized to concurrent chemoradiation, and 82% in patients randomized to radiation alone (HRs, 0.47 for sequential vs. radiation alone and 0.67 for sequential vs. concurrent; P = .026).
In the overall population, DFS was superior among patients with intermediate-risk versus high-risk factors. The 3-year DFS rates were 90% and 74%, respectively (P < .05).
Overall survival and safety
As for overall survival (OS), sequential chemoradiation showed a trend toward improvement at 5 years, compared with the other treatment groups. However, the differences were not statistically significant in either the ITT or per-protocol populations.
In the ITT population, the 5-year OS was 92% in the sequential chemoradiation arm, 89% in the concurrent chemoradiation arm, and 88% in the radiation-only arm. In the per-protocol population, the 5-year OS rates were 93%, 90%, and 88%, respectively.
Patients with intermediate-risk factors had a more favorable OS. The 5-year OS rate was 93% in patients with intermediate-risk factors and 81% in patients with high-risk factors (P < .05).
Dr. Huang noted that patients in the radiation-only arm experienced fewer grade 3-4 adverse events than the other patients. Less neutropenia, nausea, and vomiting were observed in the radiation-only arm.
There was more grade 3-4 nausea and vomiting in the concurrent chemoradiation arm than in the sequential chemoradiation arm.
However, Dr. Huang noted that “adding chemotherapy to radiation did not impact the patients’ quality of life in the long-term compared with radiation alone.
“In this study, sequential chemoradiation resulted in a better disease-free survival and a lower risk of cancer death for cervical cancer patients with adverse pathological factors,” he said. “We believe that sequential chemoradiation could be an optimal option for post-operative adjuvant treatment.”
This study was sponsored by Sun Yat-sen University in collaboration with Guangdong Provincial People’s Hospital, First Affiliated Hospital/Sun Yat-Sen University, Shenzhen People’s Hospital, and Cancer Hospital of Guangxi Medical University. Dr. Huang reported receiving honoraria, travel, accommodations, and expenses from AstraZeneca.
SOURCE: Huang H et al. ASCO 2020, Abstract 6007.
FROM ASCO 2020
Intranasal butorphanol effectively rescues from intractable itch in retrospective study
Shawn G. Kwatra, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
Dr. Kwatra, a dermatologist at Johns Hopkins University, Baltimore, where he heads a specialized pruritus clinic, presented a retrospective study of 16 such patients treated with inhaled butorphanol. All had been responsive to a minimum of four antipruritic medications.
This is one of the largest-ever reported series of patients treated with intranasal butorphanol as acute rescue therapy for intractable itch, and it provides a strong signal of efficacy, he said in an interview.
Indeed, 11 of the 16 patients reported marked improvement in their itch after introduction of short-term treatment with butorphanol nasal spray, 1 reported no improvement, and 4 were lost to follow-up.
Itch, Dermatology Life Quality Index (DLQI), and Beck Depression Inventory scores were formally measured prior to introduction of short-term inhaled butorphanol and again at follow-up appointments at 4-6 weeks. The mean self-reported itch numeric rating scale score improved from a mean of 9.8 out of a possible 10 at baseline to 4.6 at follow-up. The reduction in itch was accompanied by major improvements in quality of life: the mean DLQI score dropped from 20.2 to 10.8, while the Beck Depression Inventory score went from 22.1 – typically interpreted as an indicator of moderate depression – to 14.2.
Three patients reported insomnia and/or lightheadedness they attributed to inhaled butorphanol.
The patients with chronic refractory itch had a wide range of associated underlying diagnoses. These included primary sclerosing cholangitis, trigeminal trophic syndrome, brachioradial pruritus, neuropathic pruritus, prurigo nodularis, chronic idiopathic urticaria, chronic aquagenic pruritus, atopic dermatitis, and itch induced by programmed death–1 immune checkpoint inhibitor therapy. It will take large randomized, controlled trials to determine which of these types of chronic pruritus benefit most from intranasal butorphanol, according to Dr. Kwatra.
Since butorphanol is a narcotic analgesic ill-suited to applications other than as short-term acute rescue therapy, there is a pressing unmet need for new therapies specifically targeting chronic itch as a symptom, he added. Several promising agents are advancing through the drug development pipeline.
Dr. Kwatra reported having no financial conflicts regarding this study, conducted free of commercial support.
Shawn G. Kwatra, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
Dr. Kwatra, a dermatologist at Johns Hopkins University, Baltimore, where he heads a specialized pruritus clinic, presented a retrospective study of 16 such patients treated with inhaled butorphanol. All had been responsive to a minimum of four antipruritic medications.
This is one of the largest-ever reported series of patients treated with intranasal butorphanol as acute rescue therapy for intractable itch, and it provides a strong signal of efficacy, he said in an interview.
Indeed, 11 of the 16 patients reported marked improvement in their itch after introduction of short-term treatment with butorphanol nasal spray, 1 reported no improvement, and 4 were lost to follow-up.
Itch, Dermatology Life Quality Index (DLQI), and Beck Depression Inventory scores were formally measured prior to introduction of short-term inhaled butorphanol and again at follow-up appointments at 4-6 weeks. The mean self-reported itch numeric rating scale score improved from a mean of 9.8 out of a possible 10 at baseline to 4.6 at follow-up. The reduction in itch was accompanied by major improvements in quality of life: the mean DLQI score dropped from 20.2 to 10.8, while the Beck Depression Inventory score went from 22.1 – typically interpreted as an indicator of moderate depression – to 14.2.
Three patients reported insomnia and/or lightheadedness they attributed to inhaled butorphanol.
The patients with chronic refractory itch had a wide range of associated underlying diagnoses. These included primary sclerosing cholangitis, trigeminal trophic syndrome, brachioradial pruritus, neuropathic pruritus, prurigo nodularis, chronic idiopathic urticaria, chronic aquagenic pruritus, atopic dermatitis, and itch induced by programmed death–1 immune checkpoint inhibitor therapy. It will take large randomized, controlled trials to determine which of these types of chronic pruritus benefit most from intranasal butorphanol, according to Dr. Kwatra.
Since butorphanol is a narcotic analgesic ill-suited to applications other than as short-term acute rescue therapy, there is a pressing unmet need for new therapies specifically targeting chronic itch as a symptom, he added. Several promising agents are advancing through the drug development pipeline.
Dr. Kwatra reported having no financial conflicts regarding this study, conducted free of commercial support.
Shawn G. Kwatra, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
Dr. Kwatra, a dermatologist at Johns Hopkins University, Baltimore, where he heads a specialized pruritus clinic, presented a retrospective study of 16 such patients treated with inhaled butorphanol. All had been responsive to a minimum of four antipruritic medications.
This is one of the largest-ever reported series of patients treated with intranasal butorphanol as acute rescue therapy for intractable itch, and it provides a strong signal of efficacy, he said in an interview.
Indeed, 11 of the 16 patients reported marked improvement in their itch after introduction of short-term treatment with butorphanol nasal spray, 1 reported no improvement, and 4 were lost to follow-up.
Itch, Dermatology Life Quality Index (DLQI), and Beck Depression Inventory scores were formally measured prior to introduction of short-term inhaled butorphanol and again at follow-up appointments at 4-6 weeks. The mean self-reported itch numeric rating scale score improved from a mean of 9.8 out of a possible 10 at baseline to 4.6 at follow-up. The reduction in itch was accompanied by major improvements in quality of life: the mean DLQI score dropped from 20.2 to 10.8, while the Beck Depression Inventory score went from 22.1 – typically interpreted as an indicator of moderate depression – to 14.2.
Three patients reported insomnia and/or lightheadedness they attributed to inhaled butorphanol.
The patients with chronic refractory itch had a wide range of associated underlying diagnoses. These included primary sclerosing cholangitis, trigeminal trophic syndrome, brachioradial pruritus, neuropathic pruritus, prurigo nodularis, chronic idiopathic urticaria, chronic aquagenic pruritus, atopic dermatitis, and itch induced by programmed death–1 immune checkpoint inhibitor therapy. It will take large randomized, controlled trials to determine which of these types of chronic pruritus benefit most from intranasal butorphanol, according to Dr. Kwatra.
Since butorphanol is a narcotic analgesic ill-suited to applications other than as short-term acute rescue therapy, there is a pressing unmet need for new therapies specifically targeting chronic itch as a symptom, he added. Several promising agents are advancing through the drug development pipeline.
Dr. Kwatra reported having no financial conflicts regarding this study, conducted free of commercial support.
FROM AAD 20
Key clinical point: Intranasal butorphanol as short-term rescue therapy is a game changer for intractable itch.
Major finding: Mean itch numeric rating scale scores improved from 9.8 to 4.6.
Study details: This was a retrospective study of 16 patients who presented to a university pruritus clinic with severe chronic itch unresponsive to at least four antipruritic therapies.
Disclosures: The presenter reported having no financial conflicts regarding this study, conducted free of commercial support.
Source: Kwatra SG. AAD 20, Abstract 17132.
Immunotherapy combo improves ORR, PFS in PD-L1+ NSCLC
Patients who received tiragolumab, an anti-TIGIT antibody, in combination with atezolizumab, a PD-L1 inhibitor, had superior overall response rates (ORR) and progression-free survival (PFS), when compared with results of patients who received placebo with atezolizumab.
Melissa L. Johnson, MD, of the Sarah Cannon Research Institute in Nashville, Tenn., presented these results as part of the American Society of Clinical Oncology virtual scientific program.
Dr. Johnson explained that TIGIT is an immunomodulatory receptor present on activated T cells and natural killer cells in multiple cancers, including NSCLC.
“TIGIT inhibits T cells and natural killer cells by binding to its ligand PVR on tumor cells and antigen-presenting cells,” she said. “TIGIT expression strongly correlates with PD-1 expression, sometimes on the same tumor-infiltrating T cells in lung cancer. So the hypothesis of this trial was that anti-TIGIT antibodies, which prevent TIGIT from binding to its ligand, could restore the antitumor response and could complement the activity of anti–PD-L1/PD-1 antibodies.”
Dr. Johnson noted that combination anti–TIGIT/PD-L1 antibody treatment synergistically improved tumor control and prolonged survival over either antibody alone in preclinical models (Cancer Cell. 2014 Dec 8;26[6]:923-937). In addition, tiragolumab has been evaluated in a phase 1 study, both as monotherapy and in combination with atezolizumab, in multiple solid tumors (NCT02794571).
The phase 2 CITYSCAPE study (NCT03563716) was initiated to confirm the efficacy and safety of tiragolumab plus atezolizumab versus placebo plus atezolizumab for the first-line treatment of NSCLC, Dr. Johnson said.
CITYSCAPE enrolled 135 patients with chemotherapy-naive, PD-L1–positive, locally advanced or metastatic NSCLC. Patients did not have EGFR or ALK alterations.
Half of patients (n = 68) were randomized to receive tiragolumab at 600 mg plus atezolizumab at 1,200 mg, both given on day 1 of every 3-week cycle. The other half of patients (n = 67) were randomized to receive atezolizumab at the same dose and schedule plus placebo.
ORR and PFS
The study’s primary analysis was conducted in June 2019 at a median follow-up of 5.9 months. At that time, the ORR and PFS data showed an early benefit with tiragolumab. The ORR was 31% in the tiragolumab arm and 16% in the placebo arm. The median PFS was 5.42 months and 3.58 months, respectively (hazard ratio, 0.57).
With an additional 6 months of follow-up, the tiragolumab benefit persisted, Dr. Johnson said. The updated ORR in the intent-to-treat population was 37% in the tiragolumab arm and 21% in the placebo arm. The median PFS was 5.6 months and 3.9 months, respectively (HR, 0.58).
The tiragolumab combination showed “clinically meaningful” improvements in ORR and PFS, Dr. Johnson said. She also noted “a greater magnitude of improvement” was seen in patients with a PD-L1 tumor proportion score of 50% or greater.
There were 29 patients in each treatment arm with a PD-L1 tumor proportion score of 50% or greater. Among these patients, the ORR was 66% in the tiragolumab arm and 24% in the placebo arm. The median PFS was not reached and 4.1 months, respectively (HR, 0.30).
There were no significant differences in ORR or PFS among patients with PD-L1 tumor proportion scores below 50%, Dr. Johnson noted.
She added that duration of response and overall survival data are not yet mature and will be presented at a future conference.
Adverse events
As reported in the primary analysis, tiragolumab plus atezolizumab had a tolerable safety profile, Dr. Johnson said.
“Despite a near doubling of the median treatment duration [at the updated analysis], there were similar numbers of any-cause adverse events, grade 3-5 adverse events, and serious adverse events,” she said.
Overall, adverse events occurred in 99% of patients in the tiragolumab arm and 96% of those in the placebo arm. Rates of grade 3-5 adverse events were 48% and 44%, respectively. Rates of serious adverse events were 37% and 35%, respectively.
A higher frequency of adverse events in the tiragolumab arm was related to an increase in immune-related events, including infusion reactions, pruritus, rash, arthralgia, and nephritis. This makes sense because the patients in that group were receiving two active immunotherapies, Dr. Johnson said.
Data inspire cautious optimism
The safety and activity of tiragolumab plus atezolizumab are “to be confirmed in an ongoing phase 3 study called SKYSCRAPER-01 [NCT04294810],” Dr. Johnson said.
Invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., said the ORRs in CITYSCAPE have “generated a lot of buzz,” but she urged caution pending phase 3 results.
“While we are all excited by the data and want to see a winner, we should be careful, as speed can also crash and burn,” she said. “We have plenty of examples of promising studies that collapsed in later phase trials.”
There is room, however, for cautious optimism that the combination is a promising advance “as long as no prognostic or confounding variable is determined later on to be nonrandomly distributed between the groups to account for the difference seen,” Dr. Dy said.
She also noted that “the distribution of favorable or unfavorable mutations between the groups is unknown, and understanding this will be relevant.”
Preclinical data suggest the presence of DNM1 expression is crucial for maximizing the effect of TIGIT blockade, and tumor MHC class 1 expression appears to be reduced alongside reductions in DNM1 expression in the intratumoral natural kill cells in lung cancer specimens, Dr. Dy explained.
“Assessment of these biomarkers will be instructive,” she said. “More recent data also appear to implicate a paradoxical role of soluble CD155 or PVR ligand in actually inhibiting DNM1, so the effect of systemic TIGIT blockade may be mitigated if there is rebound increase of counterbalancing signals by increased secretion of soluble CD155, and we look forward to more data in the future regarding this.”
CITYSCAPE was sponsored by Genentech. Dr. Johnson disclosed relationships with Genentech and numerous other companies. Dr. Dy disclosed relationships with AstraZeneca, GlaxoSmithKline, Takeda, Amgen, Bristol-Myers Squibb, Regeneron, and Tesaro.
SOURCE: Rodriguez-Abreu D et al. ASCO 2020, Abstract 9503.
Patients who received tiragolumab, an anti-TIGIT antibody, in combination with atezolizumab, a PD-L1 inhibitor, had superior overall response rates (ORR) and progression-free survival (PFS), when compared with results of patients who received placebo with atezolizumab.
Melissa L. Johnson, MD, of the Sarah Cannon Research Institute in Nashville, Tenn., presented these results as part of the American Society of Clinical Oncology virtual scientific program.
Dr. Johnson explained that TIGIT is an immunomodulatory receptor present on activated T cells and natural killer cells in multiple cancers, including NSCLC.
“TIGIT inhibits T cells and natural killer cells by binding to its ligand PVR on tumor cells and antigen-presenting cells,” she said. “TIGIT expression strongly correlates with PD-1 expression, sometimes on the same tumor-infiltrating T cells in lung cancer. So the hypothesis of this trial was that anti-TIGIT antibodies, which prevent TIGIT from binding to its ligand, could restore the antitumor response and could complement the activity of anti–PD-L1/PD-1 antibodies.”
Dr. Johnson noted that combination anti–TIGIT/PD-L1 antibody treatment synergistically improved tumor control and prolonged survival over either antibody alone in preclinical models (Cancer Cell. 2014 Dec 8;26[6]:923-937). In addition, tiragolumab has been evaluated in a phase 1 study, both as monotherapy and in combination with atezolizumab, in multiple solid tumors (NCT02794571).
The phase 2 CITYSCAPE study (NCT03563716) was initiated to confirm the efficacy and safety of tiragolumab plus atezolizumab versus placebo plus atezolizumab for the first-line treatment of NSCLC, Dr. Johnson said.
CITYSCAPE enrolled 135 patients with chemotherapy-naive, PD-L1–positive, locally advanced or metastatic NSCLC. Patients did not have EGFR or ALK alterations.
Half of patients (n = 68) were randomized to receive tiragolumab at 600 mg plus atezolizumab at 1,200 mg, both given on day 1 of every 3-week cycle. The other half of patients (n = 67) were randomized to receive atezolizumab at the same dose and schedule plus placebo.
ORR and PFS
The study’s primary analysis was conducted in June 2019 at a median follow-up of 5.9 months. At that time, the ORR and PFS data showed an early benefit with tiragolumab. The ORR was 31% in the tiragolumab arm and 16% in the placebo arm. The median PFS was 5.42 months and 3.58 months, respectively (hazard ratio, 0.57).
With an additional 6 months of follow-up, the tiragolumab benefit persisted, Dr. Johnson said. The updated ORR in the intent-to-treat population was 37% in the tiragolumab arm and 21% in the placebo arm. The median PFS was 5.6 months and 3.9 months, respectively (HR, 0.58).
The tiragolumab combination showed “clinically meaningful” improvements in ORR and PFS, Dr. Johnson said. She also noted “a greater magnitude of improvement” was seen in patients with a PD-L1 tumor proportion score of 50% or greater.
There were 29 patients in each treatment arm with a PD-L1 tumor proportion score of 50% or greater. Among these patients, the ORR was 66% in the tiragolumab arm and 24% in the placebo arm. The median PFS was not reached and 4.1 months, respectively (HR, 0.30).
There were no significant differences in ORR or PFS among patients with PD-L1 tumor proportion scores below 50%, Dr. Johnson noted.
She added that duration of response and overall survival data are not yet mature and will be presented at a future conference.
Adverse events
As reported in the primary analysis, tiragolumab plus atezolizumab had a tolerable safety profile, Dr. Johnson said.
“Despite a near doubling of the median treatment duration [at the updated analysis], there were similar numbers of any-cause adverse events, grade 3-5 adverse events, and serious adverse events,” she said.
Overall, adverse events occurred in 99% of patients in the tiragolumab arm and 96% of those in the placebo arm. Rates of grade 3-5 adverse events were 48% and 44%, respectively. Rates of serious adverse events were 37% and 35%, respectively.
A higher frequency of adverse events in the tiragolumab arm was related to an increase in immune-related events, including infusion reactions, pruritus, rash, arthralgia, and nephritis. This makes sense because the patients in that group were receiving two active immunotherapies, Dr. Johnson said.
Data inspire cautious optimism
The safety and activity of tiragolumab plus atezolizumab are “to be confirmed in an ongoing phase 3 study called SKYSCRAPER-01 [NCT04294810],” Dr. Johnson said.
Invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., said the ORRs in CITYSCAPE have “generated a lot of buzz,” but she urged caution pending phase 3 results.
“While we are all excited by the data and want to see a winner, we should be careful, as speed can also crash and burn,” she said. “We have plenty of examples of promising studies that collapsed in later phase trials.”
There is room, however, for cautious optimism that the combination is a promising advance “as long as no prognostic or confounding variable is determined later on to be nonrandomly distributed between the groups to account for the difference seen,” Dr. Dy said.
She also noted that “the distribution of favorable or unfavorable mutations between the groups is unknown, and understanding this will be relevant.”
Preclinical data suggest the presence of DNM1 expression is crucial for maximizing the effect of TIGIT blockade, and tumor MHC class 1 expression appears to be reduced alongside reductions in DNM1 expression in the intratumoral natural kill cells in lung cancer specimens, Dr. Dy explained.
“Assessment of these biomarkers will be instructive,” she said. “More recent data also appear to implicate a paradoxical role of soluble CD155 or PVR ligand in actually inhibiting DNM1, so the effect of systemic TIGIT blockade may be mitigated if there is rebound increase of counterbalancing signals by increased secretion of soluble CD155, and we look forward to more data in the future regarding this.”
CITYSCAPE was sponsored by Genentech. Dr. Johnson disclosed relationships with Genentech and numerous other companies. Dr. Dy disclosed relationships with AstraZeneca, GlaxoSmithKline, Takeda, Amgen, Bristol-Myers Squibb, Regeneron, and Tesaro.
SOURCE: Rodriguez-Abreu D et al. ASCO 2020, Abstract 9503.
Patients who received tiragolumab, an anti-TIGIT antibody, in combination with atezolizumab, a PD-L1 inhibitor, had superior overall response rates (ORR) and progression-free survival (PFS), when compared with results of patients who received placebo with atezolizumab.
Melissa L. Johnson, MD, of the Sarah Cannon Research Institute in Nashville, Tenn., presented these results as part of the American Society of Clinical Oncology virtual scientific program.
Dr. Johnson explained that TIGIT is an immunomodulatory receptor present on activated T cells and natural killer cells in multiple cancers, including NSCLC.
“TIGIT inhibits T cells and natural killer cells by binding to its ligand PVR on tumor cells and antigen-presenting cells,” she said. “TIGIT expression strongly correlates with PD-1 expression, sometimes on the same tumor-infiltrating T cells in lung cancer. So the hypothesis of this trial was that anti-TIGIT antibodies, which prevent TIGIT from binding to its ligand, could restore the antitumor response and could complement the activity of anti–PD-L1/PD-1 antibodies.”
Dr. Johnson noted that combination anti–TIGIT/PD-L1 antibody treatment synergistically improved tumor control and prolonged survival over either antibody alone in preclinical models (Cancer Cell. 2014 Dec 8;26[6]:923-937). In addition, tiragolumab has been evaluated in a phase 1 study, both as monotherapy and in combination with atezolizumab, in multiple solid tumors (NCT02794571).
The phase 2 CITYSCAPE study (NCT03563716) was initiated to confirm the efficacy and safety of tiragolumab plus atezolizumab versus placebo plus atezolizumab for the first-line treatment of NSCLC, Dr. Johnson said.
CITYSCAPE enrolled 135 patients with chemotherapy-naive, PD-L1–positive, locally advanced or metastatic NSCLC. Patients did not have EGFR or ALK alterations.
Half of patients (n = 68) were randomized to receive tiragolumab at 600 mg plus atezolizumab at 1,200 mg, both given on day 1 of every 3-week cycle. The other half of patients (n = 67) were randomized to receive atezolizumab at the same dose and schedule plus placebo.
ORR and PFS
The study’s primary analysis was conducted in June 2019 at a median follow-up of 5.9 months. At that time, the ORR and PFS data showed an early benefit with tiragolumab. The ORR was 31% in the tiragolumab arm and 16% in the placebo arm. The median PFS was 5.42 months and 3.58 months, respectively (hazard ratio, 0.57).
With an additional 6 months of follow-up, the tiragolumab benefit persisted, Dr. Johnson said. The updated ORR in the intent-to-treat population was 37% in the tiragolumab arm and 21% in the placebo arm. The median PFS was 5.6 months and 3.9 months, respectively (HR, 0.58).
The tiragolumab combination showed “clinically meaningful” improvements in ORR and PFS, Dr. Johnson said. She also noted “a greater magnitude of improvement” was seen in patients with a PD-L1 tumor proportion score of 50% or greater.
There were 29 patients in each treatment arm with a PD-L1 tumor proportion score of 50% or greater. Among these patients, the ORR was 66% in the tiragolumab arm and 24% in the placebo arm. The median PFS was not reached and 4.1 months, respectively (HR, 0.30).
There were no significant differences in ORR or PFS among patients with PD-L1 tumor proportion scores below 50%, Dr. Johnson noted.
She added that duration of response and overall survival data are not yet mature and will be presented at a future conference.
Adverse events
As reported in the primary analysis, tiragolumab plus atezolizumab had a tolerable safety profile, Dr. Johnson said.
“Despite a near doubling of the median treatment duration [at the updated analysis], there were similar numbers of any-cause adverse events, grade 3-5 adverse events, and serious adverse events,” she said.
Overall, adverse events occurred in 99% of patients in the tiragolumab arm and 96% of those in the placebo arm. Rates of grade 3-5 adverse events were 48% and 44%, respectively. Rates of serious adverse events were 37% and 35%, respectively.
A higher frequency of adverse events in the tiragolumab arm was related to an increase in immune-related events, including infusion reactions, pruritus, rash, arthralgia, and nephritis. This makes sense because the patients in that group were receiving two active immunotherapies, Dr. Johnson said.
Data inspire cautious optimism
The safety and activity of tiragolumab plus atezolizumab are “to be confirmed in an ongoing phase 3 study called SKYSCRAPER-01 [NCT04294810],” Dr. Johnson said.
Invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., said the ORRs in CITYSCAPE have “generated a lot of buzz,” but she urged caution pending phase 3 results.
“While we are all excited by the data and want to see a winner, we should be careful, as speed can also crash and burn,” she said. “We have plenty of examples of promising studies that collapsed in later phase trials.”
There is room, however, for cautious optimism that the combination is a promising advance “as long as no prognostic or confounding variable is determined later on to be nonrandomly distributed between the groups to account for the difference seen,” Dr. Dy said.
She also noted that “the distribution of favorable or unfavorable mutations between the groups is unknown, and understanding this will be relevant.”
Preclinical data suggest the presence of DNM1 expression is crucial for maximizing the effect of TIGIT blockade, and tumor MHC class 1 expression appears to be reduced alongside reductions in DNM1 expression in the intratumoral natural kill cells in lung cancer specimens, Dr. Dy explained.
“Assessment of these biomarkers will be instructive,” she said. “More recent data also appear to implicate a paradoxical role of soluble CD155 or PVR ligand in actually inhibiting DNM1, so the effect of systemic TIGIT blockade may be mitigated if there is rebound increase of counterbalancing signals by increased secretion of soluble CD155, and we look forward to more data in the future regarding this.”
CITYSCAPE was sponsored by Genentech. Dr. Johnson disclosed relationships with Genentech and numerous other companies. Dr. Dy disclosed relationships with AstraZeneca, GlaxoSmithKline, Takeda, Amgen, Bristol-Myers Squibb, Regeneron, and Tesaro.
SOURCE: Rodriguez-Abreu D et al. ASCO 2020, Abstract 9503.
FROM ASCO 2020
CMSC MRI guidelines evolve into international consensus protocol
, with the hope that internationally accepted consensus guidelines will improve lagging conformity with the recommendations.
“We’ve always envisioned the guidelines as being international, but now we have harmony with the groups, so this is truly a global protocol,” Anthony Traboulsee, MD, a professor of neurology and director of the MS clinic and neuromyelitis optica clinic at the University of British Columbia in Vancouver, said in presenting the proposed updates during the virtual meeting of the CMSC.
The updates reflect the input of an international expert panel convened by the CMSC in October 2019, made up of neurologists, radiologists, magnetic resonance technologists, and imaging scientists with expertise in MS. Attendees represented groups including the European-based Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, National MS Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis.
Standardizing scans
While the mission was to review and update the current guidelines, an important overriding objective was to boost universal acceptance and improve the utilization of the protocol, which research shows is surprisingly low. According to one poster presented at the meeting, a real-world MRI dataset of 1,233 sessions showed only 8% satisfied criteria for the T1 sequence outlined in the 2018 guidelines, and only 7% satisfied criteria for the T2 sequence. “In a real-world MRI dataset of patients with MS, the conformance to the CMSC brain MRI guidelines was extremely low,” concluded the authors, who were with Icometrix, in Chicago and Belgium.
David Li, MD, also of the University of British Columbia and cochair of the MRI guideline committee, said the nonconformity has important implications. “Nonstandardized scans, with inconsistent slice thickness and gaps, nonstandardized slice acquisition (not in the subcallosal plane), and incomplete brain coverage, all contribute to scans that are difficult to compare,” he said. Those factors, “allow for assessment of new lesions and lesion activity that are invaluable for diagnosis as well as determining the effectiveness of therapy or the need for initiating/changing therapy.”
Dr. Traboulsee said the lack of adherence to guidelines may simply have to do with a mistaken perception of complexity. “Part of the challenge is MRI centers don’t realize how easy it is to implement these guidelines,” he said in presenting the proposed updates.
Dr. Traboulsee noted that the CMSC has been working with manufacturers to try to incorporate the protocol into the scanners “so that it’s just a button to press” for the MRI. “I think that will get us over a major hurdle of adaptation,” Dr. Traboulsee said. “Most radiologists said once they started using it they were really happy with it. They found they were using it beyond MS for other basic neurologic imaging, so just raising awareness and making things more of a one-step process for individuals to use will be helpful,” he said.
Repositioning consistency is key
Among key suggestions that the expert panel proposed for guideline updates include the use of the subcallosal plane for consistent repositioning, which should allow for more accuracy and consistency in the identification of lesions in MS, Dr. Traboulsee said. “A major change reflecting improvements in MRI technology is the ability to acquire high-resolution 3-D images and that’s particularly helpful with fluid attenuation inversion recovery (FLAIR) sequences, which is what we do to identify lesions,” he explained. “The repositioning along the subcallosal line is important because it allows us to easily compare studies over time. It takes very little time but allows us to prepare studies over time much more easily,” he said.
Central vein sign
Another update is the establishment of a new category of optimum plus sequences allowing for the monitoring of brain atrophy and identifying lesions with a central vein sign, which has gained high interest as a marker on 3T MRI of demyelinating plaques in MS. As described in recent research, the central vein sign shows high accuracy in differentiating between MS and non-MS lesions.
“Many people have a few white spots on neuroimaging, but with MRI so much more available around the world, many of them are being misdiagnosed with MS,” Dr. Traboulsee said. “But the central vein sign, using a very simple MRI technique, can identify lesions with a vein in the center that (distinguishes them as) MS lesions.”
Though the process is still several years from routine clinical use, the proposed update would better implement susceptibility weighted imaging, which has traditionally been used for functional MRI.
PML Surveillance
The updates also include recommendations to help in the detection of the rare but potentially serious complication of some disease-modifying therapies of progressive multifocal leukoencephalopathy (PML). “We need a very quick and comprehensive way to monitor patients for PML before symptoms develop,” Dr. Traboulsee said. “The sequences we recommended were based on expert opinion of people who have worked quite a bit with PML in MS, and if one wants to survey for PML it’s only about a 10-minute scan.”
International protocol
Corey Ford, MD, a professor of neurology and director of the MS Specialty Clinic at the University of New Mexico Health Sciences Center in Albuquerque, commented that, with imaging playing such an important role in MS, the lack of adherence to the protocol can be a significant hindrance. “MRI is the most important imaging tool we have in the diagnosing and management of MS, but ... it’s quite amazing how different the sequences that are used can be when imaging centers are asked to image someone with a diagnosis of MS, so it’s a problem,” he said.
Dr. Ford speculated that part of the problem is simply inertia at some imaging centers. “Practices will have been programmed into their protocol for a long time, so when a patient comes in for imaging regarding MS, they may [turn to] their typical sequence,” he said. “There is an inertial barrier to upgrading that sequence, which can involve testing it out on the machine, training the techs to do it that way, and interpreting it for the physician clients who requested the imaging.”
In addition, there is a lack of exposure of MS imaging guidelines in the radiology literature, Dr. Ford added. “Maybe it’s a matter of giving more presentations at meetings that include radiologists, or getting the information out through the manufacturers. I think at the end of the day it could be a combination of all of those things,” he said.
However, the CMSC collaboration could make a big difference, Dr. Ford noted. “This is where the international protocol could be important in terms of making all of this happen,” he said. “What we’re seeing is the confluence of representatives of the U.S. and European centers hash out a consensus, and if it’s international, I think that adds a lot of weight to an eventual implementation on a wider basis.”
“I think the group has done a stellar job, and we should not try to be too focused on adding everyone’s little tweak,” he noted. “If we can get a good baseline foundational imaging sequence that can be implemented worldwide, we would be much better off.”
The CMSC updated imaging guidelines are expected to be published in coming months. The most recent previous updates are available online.
Dr. Traboulsee disclosed relationships with Biogen, Chugai, Roche, Sanofi, and Teva. Dr. Ford and Dr. Li have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, with the hope that internationally accepted consensus guidelines will improve lagging conformity with the recommendations.
“We’ve always envisioned the guidelines as being international, but now we have harmony with the groups, so this is truly a global protocol,” Anthony Traboulsee, MD, a professor of neurology and director of the MS clinic and neuromyelitis optica clinic at the University of British Columbia in Vancouver, said in presenting the proposed updates during the virtual meeting of the CMSC.
The updates reflect the input of an international expert panel convened by the CMSC in October 2019, made up of neurologists, radiologists, magnetic resonance technologists, and imaging scientists with expertise in MS. Attendees represented groups including the European-based Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, National MS Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis.
Standardizing scans
While the mission was to review and update the current guidelines, an important overriding objective was to boost universal acceptance and improve the utilization of the protocol, which research shows is surprisingly low. According to one poster presented at the meeting, a real-world MRI dataset of 1,233 sessions showed only 8% satisfied criteria for the T1 sequence outlined in the 2018 guidelines, and only 7% satisfied criteria for the T2 sequence. “In a real-world MRI dataset of patients with MS, the conformance to the CMSC brain MRI guidelines was extremely low,” concluded the authors, who were with Icometrix, in Chicago and Belgium.
David Li, MD, also of the University of British Columbia and cochair of the MRI guideline committee, said the nonconformity has important implications. “Nonstandardized scans, with inconsistent slice thickness and gaps, nonstandardized slice acquisition (not in the subcallosal plane), and incomplete brain coverage, all contribute to scans that are difficult to compare,” he said. Those factors, “allow for assessment of new lesions and lesion activity that are invaluable for diagnosis as well as determining the effectiveness of therapy or the need for initiating/changing therapy.”
Dr. Traboulsee said the lack of adherence to guidelines may simply have to do with a mistaken perception of complexity. “Part of the challenge is MRI centers don’t realize how easy it is to implement these guidelines,” he said in presenting the proposed updates.
Dr. Traboulsee noted that the CMSC has been working with manufacturers to try to incorporate the protocol into the scanners “so that it’s just a button to press” for the MRI. “I think that will get us over a major hurdle of adaptation,” Dr. Traboulsee said. “Most radiologists said once they started using it they were really happy with it. They found they were using it beyond MS for other basic neurologic imaging, so just raising awareness and making things more of a one-step process for individuals to use will be helpful,” he said.
Repositioning consistency is key
Among key suggestions that the expert panel proposed for guideline updates include the use of the subcallosal plane for consistent repositioning, which should allow for more accuracy and consistency in the identification of lesions in MS, Dr. Traboulsee said. “A major change reflecting improvements in MRI technology is the ability to acquire high-resolution 3-D images and that’s particularly helpful with fluid attenuation inversion recovery (FLAIR) sequences, which is what we do to identify lesions,” he explained. “The repositioning along the subcallosal line is important because it allows us to easily compare studies over time. It takes very little time but allows us to prepare studies over time much more easily,” he said.
Central vein sign
Another update is the establishment of a new category of optimum plus sequences allowing for the monitoring of brain atrophy and identifying lesions with a central vein sign, which has gained high interest as a marker on 3T MRI of demyelinating plaques in MS. As described in recent research, the central vein sign shows high accuracy in differentiating between MS and non-MS lesions.
“Many people have a few white spots on neuroimaging, but with MRI so much more available around the world, many of them are being misdiagnosed with MS,” Dr. Traboulsee said. “But the central vein sign, using a very simple MRI technique, can identify lesions with a vein in the center that (distinguishes them as) MS lesions.”
Though the process is still several years from routine clinical use, the proposed update would better implement susceptibility weighted imaging, which has traditionally been used for functional MRI.
PML Surveillance
The updates also include recommendations to help in the detection of the rare but potentially serious complication of some disease-modifying therapies of progressive multifocal leukoencephalopathy (PML). “We need a very quick and comprehensive way to monitor patients for PML before symptoms develop,” Dr. Traboulsee said. “The sequences we recommended were based on expert opinion of people who have worked quite a bit with PML in MS, and if one wants to survey for PML it’s only about a 10-minute scan.”
International protocol
Corey Ford, MD, a professor of neurology and director of the MS Specialty Clinic at the University of New Mexico Health Sciences Center in Albuquerque, commented that, with imaging playing such an important role in MS, the lack of adherence to the protocol can be a significant hindrance. “MRI is the most important imaging tool we have in the diagnosing and management of MS, but ... it’s quite amazing how different the sequences that are used can be when imaging centers are asked to image someone with a diagnosis of MS, so it’s a problem,” he said.
Dr. Ford speculated that part of the problem is simply inertia at some imaging centers. “Practices will have been programmed into their protocol for a long time, so when a patient comes in for imaging regarding MS, they may [turn to] their typical sequence,” he said. “There is an inertial barrier to upgrading that sequence, which can involve testing it out on the machine, training the techs to do it that way, and interpreting it for the physician clients who requested the imaging.”
In addition, there is a lack of exposure of MS imaging guidelines in the radiology literature, Dr. Ford added. “Maybe it’s a matter of giving more presentations at meetings that include radiologists, or getting the information out through the manufacturers. I think at the end of the day it could be a combination of all of those things,” he said.
However, the CMSC collaboration could make a big difference, Dr. Ford noted. “This is where the international protocol could be important in terms of making all of this happen,” he said. “What we’re seeing is the confluence of representatives of the U.S. and European centers hash out a consensus, and if it’s international, I think that adds a lot of weight to an eventual implementation on a wider basis.”
“I think the group has done a stellar job, and we should not try to be too focused on adding everyone’s little tweak,” he noted. “If we can get a good baseline foundational imaging sequence that can be implemented worldwide, we would be much better off.”
The CMSC updated imaging guidelines are expected to be published in coming months. The most recent previous updates are available online.
Dr. Traboulsee disclosed relationships with Biogen, Chugai, Roche, Sanofi, and Teva. Dr. Ford and Dr. Li have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, with the hope that internationally accepted consensus guidelines will improve lagging conformity with the recommendations.
“We’ve always envisioned the guidelines as being international, but now we have harmony with the groups, so this is truly a global protocol,” Anthony Traboulsee, MD, a professor of neurology and director of the MS clinic and neuromyelitis optica clinic at the University of British Columbia in Vancouver, said in presenting the proposed updates during the virtual meeting of the CMSC.
The updates reflect the input of an international expert panel convened by the CMSC in October 2019, made up of neurologists, radiologists, magnetic resonance technologists, and imaging scientists with expertise in MS. Attendees represented groups including the European-based Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, National MS Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis.
Standardizing scans
While the mission was to review and update the current guidelines, an important overriding objective was to boost universal acceptance and improve the utilization of the protocol, which research shows is surprisingly low. According to one poster presented at the meeting, a real-world MRI dataset of 1,233 sessions showed only 8% satisfied criteria for the T1 sequence outlined in the 2018 guidelines, and only 7% satisfied criteria for the T2 sequence. “In a real-world MRI dataset of patients with MS, the conformance to the CMSC brain MRI guidelines was extremely low,” concluded the authors, who were with Icometrix, in Chicago and Belgium.
David Li, MD, also of the University of British Columbia and cochair of the MRI guideline committee, said the nonconformity has important implications. “Nonstandardized scans, with inconsistent slice thickness and gaps, nonstandardized slice acquisition (not in the subcallosal plane), and incomplete brain coverage, all contribute to scans that are difficult to compare,” he said. Those factors, “allow for assessment of new lesions and lesion activity that are invaluable for diagnosis as well as determining the effectiveness of therapy or the need for initiating/changing therapy.”
Dr. Traboulsee said the lack of adherence to guidelines may simply have to do with a mistaken perception of complexity. “Part of the challenge is MRI centers don’t realize how easy it is to implement these guidelines,” he said in presenting the proposed updates.
Dr. Traboulsee noted that the CMSC has been working with manufacturers to try to incorporate the protocol into the scanners “so that it’s just a button to press” for the MRI. “I think that will get us over a major hurdle of adaptation,” Dr. Traboulsee said. “Most radiologists said once they started using it they were really happy with it. They found they were using it beyond MS for other basic neurologic imaging, so just raising awareness and making things more of a one-step process for individuals to use will be helpful,” he said.
Repositioning consistency is key
Among key suggestions that the expert panel proposed for guideline updates include the use of the subcallosal plane for consistent repositioning, which should allow for more accuracy and consistency in the identification of lesions in MS, Dr. Traboulsee said. “A major change reflecting improvements in MRI technology is the ability to acquire high-resolution 3-D images and that’s particularly helpful with fluid attenuation inversion recovery (FLAIR) sequences, which is what we do to identify lesions,” he explained. “The repositioning along the subcallosal line is important because it allows us to easily compare studies over time. It takes very little time but allows us to prepare studies over time much more easily,” he said.
Central vein sign
Another update is the establishment of a new category of optimum plus sequences allowing for the monitoring of brain atrophy and identifying lesions with a central vein sign, which has gained high interest as a marker on 3T MRI of demyelinating plaques in MS. As described in recent research, the central vein sign shows high accuracy in differentiating between MS and non-MS lesions.
“Many people have a few white spots on neuroimaging, but with MRI so much more available around the world, many of them are being misdiagnosed with MS,” Dr. Traboulsee said. “But the central vein sign, using a very simple MRI technique, can identify lesions with a vein in the center that (distinguishes them as) MS lesions.”
Though the process is still several years from routine clinical use, the proposed update would better implement susceptibility weighted imaging, which has traditionally been used for functional MRI.
PML Surveillance
The updates also include recommendations to help in the detection of the rare but potentially serious complication of some disease-modifying therapies of progressive multifocal leukoencephalopathy (PML). “We need a very quick and comprehensive way to monitor patients for PML before symptoms develop,” Dr. Traboulsee said. “The sequences we recommended were based on expert opinion of people who have worked quite a bit with PML in MS, and if one wants to survey for PML it’s only about a 10-minute scan.”
International protocol
Corey Ford, MD, a professor of neurology and director of the MS Specialty Clinic at the University of New Mexico Health Sciences Center in Albuquerque, commented that, with imaging playing such an important role in MS, the lack of adherence to the protocol can be a significant hindrance. “MRI is the most important imaging tool we have in the diagnosing and management of MS, but ... it’s quite amazing how different the sequences that are used can be when imaging centers are asked to image someone with a diagnosis of MS, so it’s a problem,” he said.
Dr. Ford speculated that part of the problem is simply inertia at some imaging centers. “Practices will have been programmed into their protocol for a long time, so when a patient comes in for imaging regarding MS, they may [turn to] their typical sequence,” he said. “There is an inertial barrier to upgrading that sequence, which can involve testing it out on the machine, training the techs to do it that way, and interpreting it for the physician clients who requested the imaging.”
In addition, there is a lack of exposure of MS imaging guidelines in the radiology literature, Dr. Ford added. “Maybe it’s a matter of giving more presentations at meetings that include radiologists, or getting the information out through the manufacturers. I think at the end of the day it could be a combination of all of those things,” he said.
However, the CMSC collaboration could make a big difference, Dr. Ford noted. “This is where the international protocol could be important in terms of making all of this happen,” he said. “What we’re seeing is the confluence of representatives of the U.S. and European centers hash out a consensus, and if it’s international, I think that adds a lot of weight to an eventual implementation on a wider basis.”
“I think the group has done a stellar job, and we should not try to be too focused on adding everyone’s little tweak,” he noted. “If we can get a good baseline foundational imaging sequence that can be implemented worldwide, we would be much better off.”
The CMSC updated imaging guidelines are expected to be published in coming months. The most recent previous updates are available online.
Dr. Traboulsee disclosed relationships with Biogen, Chugai, Roche, Sanofi, and Teva. Dr. Ford and Dr. Li have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
From CMSC 2020
For urban-based African Americans, proximity to a dermatologist varies by ZIP code
Urban ZIP codes with higher percentages of African American people tend to have fewer dermatologists. In these areas, dermatologists are not able meet the populations’ needs, based on the suggested ratio of patients per dermatologist.
The findings come from an analysis which used U.S. Census data to compare dermatologists’ distribution in urban ZIP codes with high and low representation of African Americans.
“It has been demonstrated that there is a non-uniform geographic distribution of dermatologists, in which they tend to practice in urban settings,” the study’s first author, Nathan Vengalil, MD, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “Furthermore, it is also an unfortunate reality that African Americans suffer from inferior access to care compared to whites across health care. The same is true within dermatology; for example, African Americans face higher morbidity and mortality from melanoma, compared to their white counterparts.”
For the current study, Dr. Vengalil, a recent graduate of the University of Michigan, Ann Arbor, and associates in the university’s department of dermatology drew from 2010 U.S. Census data to identify ZIP codes with populations of 25,000 people and greater, because these should have at least one dermatologist to care for a community of that size (JAMA Dermatology 2017;153[5]:472-3).
Next, they ordered these ZIP codes from low to high concentrations of African American people. Those that fell in the 15th percentile or fewer were categorized as “low” (a total of 370 ZIP codes), while those that fell in the 85th percentile or higher were categorized as “high” (a total of 443 ZIP codes). Following this, the Definitive Healthcare provider database was used to identify the number of dermatologists practicing within each ZIP code and to calculate the average number of people per dermatologist in the “low” and “high” categories.
The researchers found that ZIP codes with high percentage of African American people have an average of 1.02 dermatologists (1 per 39,367 people), which is below the recommended limit of 1 per 25,000 people. Meanwhile, ZIP codes with a low percentage of African American people averaged 2.84 dermatologists (1 per 14,000 people), which is above the adequate limit. “ZIP codes with a low percentage of African Americans had, on average, almost three times more dermatologists than ZIP codes with a high percentage of American Americans,” Dr. Vengalil said. “This means that predominantly African American urban communities may face consequences of low provider availability including longer waits times, decreased diagnosis of skin cancer, and worse health care outcomes.”
He acknowledged certain limitations of the study, including the fact that it focused only on the distribution of dermatologists to assess communities’ access to dermatologic care. “It would be interesting to measure how much mid-level providers such as nurse practitioners and physician assistants are able to compensate for the low number of dermatologists in urban ZIP codes with high numbers of African Americans,” Dr. Vengalil said.
The study’s findings suggest that the distribution of dermatologists is not uniform even within the urban environment, especially when comparing areas with different representations of African American persons. “This reveals that lack of provider proximity may contribute to barriers that urban African Americans face in accessing dermatologic care,” he concluded. “Looking toward the future, it will be important to incentivize the development of practice locations in urban African American communities to combat the health disparities of our most underserved patients.”
The study’s other authors were Mio Nakamura, MD, MS, and Yolanda Helfrich, MD. The researchers reported having no financial disclosures.
SOURCE: Vengalil N et al. AAD 20, abstract 16772.
Urban ZIP codes with higher percentages of African American people tend to have fewer dermatologists. In these areas, dermatologists are not able meet the populations’ needs, based on the suggested ratio of patients per dermatologist.
The findings come from an analysis which used U.S. Census data to compare dermatologists’ distribution in urban ZIP codes with high and low representation of African Americans.
“It has been demonstrated that there is a non-uniform geographic distribution of dermatologists, in which they tend to practice in urban settings,” the study’s first author, Nathan Vengalil, MD, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “Furthermore, it is also an unfortunate reality that African Americans suffer from inferior access to care compared to whites across health care. The same is true within dermatology; for example, African Americans face higher morbidity and mortality from melanoma, compared to their white counterparts.”
For the current study, Dr. Vengalil, a recent graduate of the University of Michigan, Ann Arbor, and associates in the university’s department of dermatology drew from 2010 U.S. Census data to identify ZIP codes with populations of 25,000 people and greater, because these should have at least one dermatologist to care for a community of that size (JAMA Dermatology 2017;153[5]:472-3).
Next, they ordered these ZIP codes from low to high concentrations of African American people. Those that fell in the 15th percentile or fewer were categorized as “low” (a total of 370 ZIP codes), while those that fell in the 85th percentile or higher were categorized as “high” (a total of 443 ZIP codes). Following this, the Definitive Healthcare provider database was used to identify the number of dermatologists practicing within each ZIP code and to calculate the average number of people per dermatologist in the “low” and “high” categories.
The researchers found that ZIP codes with high percentage of African American people have an average of 1.02 dermatologists (1 per 39,367 people), which is below the recommended limit of 1 per 25,000 people. Meanwhile, ZIP codes with a low percentage of African American people averaged 2.84 dermatologists (1 per 14,000 people), which is above the adequate limit. “ZIP codes with a low percentage of African Americans had, on average, almost three times more dermatologists than ZIP codes with a high percentage of American Americans,” Dr. Vengalil said. “This means that predominantly African American urban communities may face consequences of low provider availability including longer waits times, decreased diagnosis of skin cancer, and worse health care outcomes.”
He acknowledged certain limitations of the study, including the fact that it focused only on the distribution of dermatologists to assess communities’ access to dermatologic care. “It would be interesting to measure how much mid-level providers such as nurse practitioners and physician assistants are able to compensate for the low number of dermatologists in urban ZIP codes with high numbers of African Americans,” Dr. Vengalil said.
The study’s findings suggest that the distribution of dermatologists is not uniform even within the urban environment, especially when comparing areas with different representations of African American persons. “This reveals that lack of provider proximity may contribute to barriers that urban African Americans face in accessing dermatologic care,” he concluded. “Looking toward the future, it will be important to incentivize the development of practice locations in urban African American communities to combat the health disparities of our most underserved patients.”
The study’s other authors were Mio Nakamura, MD, MS, and Yolanda Helfrich, MD. The researchers reported having no financial disclosures.
SOURCE: Vengalil N et al. AAD 20, abstract 16772.
Urban ZIP codes with higher percentages of African American people tend to have fewer dermatologists. In these areas, dermatologists are not able meet the populations’ needs, based on the suggested ratio of patients per dermatologist.
The findings come from an analysis which used U.S. Census data to compare dermatologists’ distribution in urban ZIP codes with high and low representation of African Americans.
“It has been demonstrated that there is a non-uniform geographic distribution of dermatologists, in which they tend to practice in urban settings,” the study’s first author, Nathan Vengalil, MD, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “Furthermore, it is also an unfortunate reality that African Americans suffer from inferior access to care compared to whites across health care. The same is true within dermatology; for example, African Americans face higher morbidity and mortality from melanoma, compared to their white counterparts.”
For the current study, Dr. Vengalil, a recent graduate of the University of Michigan, Ann Arbor, and associates in the university’s department of dermatology drew from 2010 U.S. Census data to identify ZIP codes with populations of 25,000 people and greater, because these should have at least one dermatologist to care for a community of that size (JAMA Dermatology 2017;153[5]:472-3).
Next, they ordered these ZIP codes from low to high concentrations of African American people. Those that fell in the 15th percentile or fewer were categorized as “low” (a total of 370 ZIP codes), while those that fell in the 85th percentile or higher were categorized as “high” (a total of 443 ZIP codes). Following this, the Definitive Healthcare provider database was used to identify the number of dermatologists practicing within each ZIP code and to calculate the average number of people per dermatologist in the “low” and “high” categories.
The researchers found that ZIP codes with high percentage of African American people have an average of 1.02 dermatologists (1 per 39,367 people), which is below the recommended limit of 1 per 25,000 people. Meanwhile, ZIP codes with a low percentage of African American people averaged 2.84 dermatologists (1 per 14,000 people), which is above the adequate limit. “ZIP codes with a low percentage of African Americans had, on average, almost three times more dermatologists than ZIP codes with a high percentage of American Americans,” Dr. Vengalil said. “This means that predominantly African American urban communities may face consequences of low provider availability including longer waits times, decreased diagnosis of skin cancer, and worse health care outcomes.”
He acknowledged certain limitations of the study, including the fact that it focused only on the distribution of dermatologists to assess communities’ access to dermatologic care. “It would be interesting to measure how much mid-level providers such as nurse practitioners and physician assistants are able to compensate for the low number of dermatologists in urban ZIP codes with high numbers of African Americans,” Dr. Vengalil said.
The study’s findings suggest that the distribution of dermatologists is not uniform even within the urban environment, especially when comparing areas with different representations of African American persons. “This reveals that lack of provider proximity may contribute to barriers that urban African Americans face in accessing dermatologic care,” he concluded. “Looking toward the future, it will be important to incentivize the development of practice locations in urban African American communities to combat the health disparities of our most underserved patients.”
The study’s other authors were Mio Nakamura, MD, MS, and Yolanda Helfrich, MD. The researchers reported having no financial disclosures.
SOURCE: Vengalil N et al. AAD 20, abstract 16772.
FROM AAD 20
Increased hypothyroidism risk seen in young men with HS
Anna Figueiredo, MD, declared at the virtual annual meeting of the American Academy of Dermatology.
The surprise about this finding from a large retrospective case-control study stems from the fact that the elevated risk for hypothyroidism didn’t also extend to younger women with hidradenitis suppurativa (HS) nor to patients older than 40 years of either gender, explained Dr. Figueiredo of the department of dermatology at Northwestern University, Chicago.
She presented a retrospective case-control study based on information extracted from a medical records database of more than 8 million Midwestern adults. Among nearly 141,000 dermatology patients with follow-up in the database for at least 1 year, there were 405 HS patients aged 18-40 years and 327 aged 41-89.
In an age-matched comparison with the dermatology patients without HS, the younger HS cohort was at a significant 1.52-fold increased risk for comorbid hypothyroidism. Upon further stratification by sex, only the younger men with HS were at increased risk. Those patients were at 3.95-fold greater risk for having a diagnosis of hypothyroidism than were age-matched younger male dermatology patients.
Both younger and older HS patients were at numerically increased risk for being diagnosed with hyperthyroidism; however, this difference didn’t approach statistical significance because there were so few cases: a total of just eight in the HS population across the full age spectrum.
Hidradenitis suppurativa is a chronic inflammatory disease with an estimated prevalence of up to 4% in the United States. Growing evidence suggests it is an immune-mediated disorder because the tumor necrosis factor inhibitor adalimumab (Humira) has been approved for treatment of HS.
Thyroid disease is also often autoimmune-mediated, but its relationship with HS hasn’t been extensively examined. A recent meta-analysis of five case-control studies concluded that HS was associated with a 1.36-fold increased risk of thyroid disease; however, the Nepalese investigators didn’t distinguish between hypo- and hyperthyroidism (J Am Acad Dermatol. 2020 Feb;82[2]:491-3).
Dr. Figueiredo reported having no financial conflicts regarding her study, which was without commercial support.
Anna Figueiredo, MD, declared at the virtual annual meeting of the American Academy of Dermatology.
The surprise about this finding from a large retrospective case-control study stems from the fact that the elevated risk for hypothyroidism didn’t also extend to younger women with hidradenitis suppurativa (HS) nor to patients older than 40 years of either gender, explained Dr. Figueiredo of the department of dermatology at Northwestern University, Chicago.
She presented a retrospective case-control study based on information extracted from a medical records database of more than 8 million Midwestern adults. Among nearly 141,000 dermatology patients with follow-up in the database for at least 1 year, there were 405 HS patients aged 18-40 years and 327 aged 41-89.
In an age-matched comparison with the dermatology patients without HS, the younger HS cohort was at a significant 1.52-fold increased risk for comorbid hypothyroidism. Upon further stratification by sex, only the younger men with HS were at increased risk. Those patients were at 3.95-fold greater risk for having a diagnosis of hypothyroidism than were age-matched younger male dermatology patients.
Both younger and older HS patients were at numerically increased risk for being diagnosed with hyperthyroidism; however, this difference didn’t approach statistical significance because there were so few cases: a total of just eight in the HS population across the full age spectrum.
Hidradenitis suppurativa is a chronic inflammatory disease with an estimated prevalence of up to 4% in the United States. Growing evidence suggests it is an immune-mediated disorder because the tumor necrosis factor inhibitor adalimumab (Humira) has been approved for treatment of HS.
Thyroid disease is also often autoimmune-mediated, but its relationship with HS hasn’t been extensively examined. A recent meta-analysis of five case-control studies concluded that HS was associated with a 1.36-fold increased risk of thyroid disease; however, the Nepalese investigators didn’t distinguish between hypo- and hyperthyroidism (J Am Acad Dermatol. 2020 Feb;82[2]:491-3).
Dr. Figueiredo reported having no financial conflicts regarding her study, which was without commercial support.
Anna Figueiredo, MD, declared at the virtual annual meeting of the American Academy of Dermatology.
The surprise about this finding from a large retrospective case-control study stems from the fact that the elevated risk for hypothyroidism didn’t also extend to younger women with hidradenitis suppurativa (HS) nor to patients older than 40 years of either gender, explained Dr. Figueiredo of the department of dermatology at Northwestern University, Chicago.
She presented a retrospective case-control study based on information extracted from a medical records database of more than 8 million Midwestern adults. Among nearly 141,000 dermatology patients with follow-up in the database for at least 1 year, there were 405 HS patients aged 18-40 years and 327 aged 41-89.
In an age-matched comparison with the dermatology patients without HS, the younger HS cohort was at a significant 1.52-fold increased risk for comorbid hypothyroidism. Upon further stratification by sex, only the younger men with HS were at increased risk. Those patients were at 3.95-fold greater risk for having a diagnosis of hypothyroidism than were age-matched younger male dermatology patients.
Both younger and older HS patients were at numerically increased risk for being diagnosed with hyperthyroidism; however, this difference didn’t approach statistical significance because there were so few cases: a total of just eight in the HS population across the full age spectrum.
Hidradenitis suppurativa is a chronic inflammatory disease with an estimated prevalence of up to 4% in the United States. Growing evidence suggests it is an immune-mediated disorder because the tumor necrosis factor inhibitor adalimumab (Humira) has been approved for treatment of HS.
Thyroid disease is also often autoimmune-mediated, but its relationship with HS hasn’t been extensively examined. A recent meta-analysis of five case-control studies concluded that HS was associated with a 1.36-fold increased risk of thyroid disease; however, the Nepalese investigators didn’t distinguish between hypo- and hyperthyroidism (J Am Acad Dermatol. 2020 Feb;82[2]:491-3).
Dr. Figueiredo reported having no financial conflicts regarding her study, which was without commercial support.
FROM AAD 20
Belimumab safely improved renal function in lupus nephritis patients
compared with control patients who only received standard therapy, in a randomized, multicenter trial with 446 evaluable patients, a finding that may help extend this treatment to a new group of lupus patients.
“The largest” treatment study of lupus nephritis reported to date showed that belimumab, approved by the Food and Drug Administration in 2011 for treating patients with systemic lupus erythematosus (SLE), administered at a standard dosage of 10 mg intravenously every 4 weeks, “significantly improved multiple lupus nephritis renal responses versus standard therapy alone while maintaining an acceptable safety profile,” Richard A. Furie, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.
The study’s primary endpoint was a composite measure that Dr. Furie and associates called the Primary Endpoint Renal Response, which required patients to have achieved a urinary protein-to-creatinine ratio of 0.7 or less (compared with an enrollment level of 1.0 or greater), an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 kg/m2 and no more than 20% below its preflare level, and continuation on the assigned treatment regimen. After 104 weeks on this treatment, which followed a 60-day induction phase that included treatment with a high-dose glucocorticoid, the percentages of patients who met the Primary Endpoint Renal Response criteria were 32% in the control arm who received standard treatment at the discretion of their treating clinicians plus placebo infusions and 43% in patients who received belimumab infusions in addition to their standard care. This calculated out to a 55% relative increase in this response with belimumab, a statistically significant result, reported Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., and chief of rheumatology at Northwell Health in Manhasset, N.Y.
Patients who received belimumab also had similar and statistically significant levels of improvement for several secondary endpoints, including one called Complete Renal Response, which required a protein-to-creatinine ratio of no greater than 0.5, an eGFR of at least 90 mL/min per 1.73 kg/m2 and no more than 10% below its preflare level, and maintaining the assigned treatment. The Complete Renal Response after 104 weeks was 20% among control patients and 30% among those maintained on belimumab, a 74% relative improvement that was statistically significant. The total percentage of patients with any renal-related event after 104 weeks was 28% among the control patients and 16% among those who received belimumab, a statistically significant difference.
“The fact that the primary and all key secondary endpoints were successfully attained is a major accomplishment in lupus nephritis as well as in any SLE study,” Dr. Furie said in an interview. The study’s 2-year design “provided insight into the durability of the response,” and the steady divergence of the endpoint events in the two study arms beginning after about 24 weeks into the randomized phase “provided data regarding the rapidity of onset of action.” Collectively, the endpoints “mimic our real-life treatment goals: reduce disease activity, prevent flares, preserve renal function, lower steroid treatment, and do it all safely,” he concluded.
Results confirm benefit to subset of patients
“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.
The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
Thoughts on current and future use of belimumab
The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.
“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.
“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.
“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.
BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.
SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.
compared with control patients who only received standard therapy, in a randomized, multicenter trial with 446 evaluable patients, a finding that may help extend this treatment to a new group of lupus patients.
“The largest” treatment study of lupus nephritis reported to date showed that belimumab, approved by the Food and Drug Administration in 2011 for treating patients with systemic lupus erythematosus (SLE), administered at a standard dosage of 10 mg intravenously every 4 weeks, “significantly improved multiple lupus nephritis renal responses versus standard therapy alone while maintaining an acceptable safety profile,” Richard A. Furie, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.
The study’s primary endpoint was a composite measure that Dr. Furie and associates called the Primary Endpoint Renal Response, which required patients to have achieved a urinary protein-to-creatinine ratio of 0.7 or less (compared with an enrollment level of 1.0 or greater), an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 kg/m2 and no more than 20% below its preflare level, and continuation on the assigned treatment regimen. After 104 weeks on this treatment, which followed a 60-day induction phase that included treatment with a high-dose glucocorticoid, the percentages of patients who met the Primary Endpoint Renal Response criteria were 32% in the control arm who received standard treatment at the discretion of their treating clinicians plus placebo infusions and 43% in patients who received belimumab infusions in addition to their standard care. This calculated out to a 55% relative increase in this response with belimumab, a statistically significant result, reported Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., and chief of rheumatology at Northwell Health in Manhasset, N.Y.
Patients who received belimumab also had similar and statistically significant levels of improvement for several secondary endpoints, including one called Complete Renal Response, which required a protein-to-creatinine ratio of no greater than 0.5, an eGFR of at least 90 mL/min per 1.73 kg/m2 and no more than 10% below its preflare level, and maintaining the assigned treatment. The Complete Renal Response after 104 weeks was 20% among control patients and 30% among those maintained on belimumab, a 74% relative improvement that was statistically significant. The total percentage of patients with any renal-related event after 104 weeks was 28% among the control patients and 16% among those who received belimumab, a statistically significant difference.
“The fact that the primary and all key secondary endpoints were successfully attained is a major accomplishment in lupus nephritis as well as in any SLE study,” Dr. Furie said in an interview. The study’s 2-year design “provided insight into the durability of the response,” and the steady divergence of the endpoint events in the two study arms beginning after about 24 weeks into the randomized phase “provided data regarding the rapidity of onset of action.” Collectively, the endpoints “mimic our real-life treatment goals: reduce disease activity, prevent flares, preserve renal function, lower steroid treatment, and do it all safely,” he concluded.
Results confirm benefit to subset of patients
“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.
The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
Thoughts on current and future use of belimumab
The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.
“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.
“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.
“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.
BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.
SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.
compared with control patients who only received standard therapy, in a randomized, multicenter trial with 446 evaluable patients, a finding that may help extend this treatment to a new group of lupus patients.
“The largest” treatment study of lupus nephritis reported to date showed that belimumab, approved by the Food and Drug Administration in 2011 for treating patients with systemic lupus erythematosus (SLE), administered at a standard dosage of 10 mg intravenously every 4 weeks, “significantly improved multiple lupus nephritis renal responses versus standard therapy alone while maintaining an acceptable safety profile,” Richard A. Furie, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.
The study’s primary endpoint was a composite measure that Dr. Furie and associates called the Primary Endpoint Renal Response, which required patients to have achieved a urinary protein-to-creatinine ratio of 0.7 or less (compared with an enrollment level of 1.0 or greater), an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 kg/m2 and no more than 20% below its preflare level, and continuation on the assigned treatment regimen. After 104 weeks on this treatment, which followed a 60-day induction phase that included treatment with a high-dose glucocorticoid, the percentages of patients who met the Primary Endpoint Renal Response criteria were 32% in the control arm who received standard treatment at the discretion of their treating clinicians plus placebo infusions and 43% in patients who received belimumab infusions in addition to their standard care. This calculated out to a 55% relative increase in this response with belimumab, a statistically significant result, reported Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., and chief of rheumatology at Northwell Health in Manhasset, N.Y.
Patients who received belimumab also had similar and statistically significant levels of improvement for several secondary endpoints, including one called Complete Renal Response, which required a protein-to-creatinine ratio of no greater than 0.5, an eGFR of at least 90 mL/min per 1.73 kg/m2 and no more than 10% below its preflare level, and maintaining the assigned treatment. The Complete Renal Response after 104 weeks was 20% among control patients and 30% among those maintained on belimumab, a 74% relative improvement that was statistically significant. The total percentage of patients with any renal-related event after 104 weeks was 28% among the control patients and 16% among those who received belimumab, a statistically significant difference.
“The fact that the primary and all key secondary endpoints were successfully attained is a major accomplishment in lupus nephritis as well as in any SLE study,” Dr. Furie said in an interview. The study’s 2-year design “provided insight into the durability of the response,” and the steady divergence of the endpoint events in the two study arms beginning after about 24 weeks into the randomized phase “provided data regarding the rapidity of onset of action.” Collectively, the endpoints “mimic our real-life treatment goals: reduce disease activity, prevent flares, preserve renal function, lower steroid treatment, and do it all safely,” he concluded.
Results confirm benefit to subset of patients
“Belimumab is a safe and effective treatment for a significant subset of patients with lupus. We already knew that. Now we have even more confirmation,” commented Joan T. Merrill, MD, a professor of medicine at the University of Oklahoma Health Sciences Center and a rheumatologist who specializes in SLE at the Oklahoma Medical Research Foundation, both in Oklahoma City. “There have already been at least four international trials demonstrating belimumab’s efficacy in general lupus. Some patients in these earlier trials had nephritis, so it should not be surprising to see similar results in a trial restricted to patients with active nephritis, given the drug’s mechanism of action. Belimumab has repeatedly shown early and sustained benefits above what background treatments achieve, and belimumab has also proven to be safe to add to standard-of-care treatments,” she said in an interview.
The BLISS-LN (Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis) study enrolled patients at any of 118 centers in 20 countries, including the United States. All patients enrolled in the trial were adults with biopsy-confirmed, clinically active lupus nephritis and a urinary protein-to-creatinine ratio of at least 1.0, and need for induction therapy. The 60-day induction run-in phase began with high-dose glucocorticoids plus either cyclophosphamide or mycophenolate mofetil (CellCept), followed by maintenance on low-dose glucocorticoids and either azathioprine or mycophenolate mofetil. Nearly three-quarters of patients received mycophenolate mofetil–based induction. Once treatment with either belimumab or placebo began in the study’s main phase, the glucocorticoid dosage had to drop with tapering to no more than 10 mg/day within 24 weeks or the patient was considered a treatment failure.
Thoughts on current and future use of belimumab
The current labeled indication for belimumab is for “treatment of patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy,” an inclusive SLE population, but the label also adds this caveat: “Limitations of use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.” According to Dr. Furie’s report, GlaxoSmithKline, the company that markets belimumab, plans to seek a labeled indication for lupus nephritis for the drug during 2020.
“I doubt the drug is widely used as yet in clinical practice for lupus nephritis,” although it is being prescribed to selected SLE patients in current, routine practice, said Dr. Merrill, a coinvestigator on some belimumab studies. What also remains unknown is the efficacy of belimumab monotherapy. “We don’t know which subset of patients might benefit from belimumab alone,” she noted. Nor is it known whether belimumab treatment of patients with SLE but without lupus nephritis will forestall later development of lupus nephritis.
“With the introduction of the subcutaneous formulation a few years ago, there has been greater belimumab use” overall in patients with SLE, said Dr. Furie, and with a safety and efficacy record now established in five separate, reported studies in addition to the new BLISS-LN study: BLISS-52, BLISS-76, BLISS-SC, BLISS-NE ASIA, and PLUTO. “The pivotal studies [BLISS-52 and BLISS-76] were done in patients with SLE but without nephritis in need of aggressive induction therapy. About 15% of the trial cohorts had low-level renal involvement,” and post hoc analyses suggested that the benefit in those patients was similar to patients without renal involvement, which led to the BLISS-LN study. “In theory, no SLE patients with high-level nephritis should be on belimumab at this time,” based on its labeling, although some SLE patients with low-level renal disease may now receive the drug because they also have other affected organs, such as skin and joints, Dr. Furie said.
“These are encouraging results,” commented George K. Bertsias, MD, a rheumatologist and SLE specialist at the University of Crete in Heraklion, Greece. He particularly cited the “significant effect from add-on belimumab” on top of treatment with mycophenolate mofetil, an “established and effective treatment for lupus nephritis. The data provide additional evidence for the efficacy of belimumab in SLE, and also in lupus nephritis,” he said in an interview, and “having an official labeled indication for active nephritis will enhance use of the drug” in such patients. “Considering the favorable effects of the drug on SLE, especially preventing major flares, and on lupus nephritis it is possible that the drug will be particularly suitable for SLE patients who are at high risk for developing lupus nephritis, although such an effect remains to be determined.” Until now, belimumab has generally been prescribed to SLE patients who have disease manifestations in organs outside of the kidneys, he noted.
BLISS-LN was sponsored by GlaxoSmithKline. Dr. Furie is a consultant to and has received research funding from GlaxoSmithKline, and several of the study’s coauthors are employees of the company. Dr. Merrill has been a consultant to GlaxoSmithKline as well as to several other companies and has been a coinvestigator on belimumab studies. Dr. Bertsias has been a consultant to Novartis and has received research funding from GlaxoSmithKline.
SOURCE: Furie RA et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:103, Abstract OP0164.
FROM THE EULAR 2020 E-CONGRESS
More phase 3 data reported for abrocitinib for atopic dermatitis
Melinda Gooderham, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The positive results of this 391-patient, international, randomized, double-blind, placebo-controlled clinical trial mirror those previously reported in the identically designed JADE-MONO-1 pivotal phase 3 trial, noted Dr. Gooderham, medical director of the SKiN Centre for Dermatology and a dermatologist at Queen’s University in Kingston, Ont.
Participants in JADE-MONO-2 were randomized 2:2:1 to abrocitinib at 200 mg once daily, 100 mg once daily, or placebo for 12 weeks. The coprimary endpoint of skin clearance as reflected in an Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with an improvement of at least two grades at week 12 was achieved in 38.1% and 28.4% of patients on 200 and 100 mg of the JAK-1 inhibitor, respectively, compared with 9.1% of placebo-treated controls. The other coprimary endpoint – significant improvement in disease extent as defined by at least a 75% reduction from baseline in Eczema Area and Severity Index (EASI-75 response) at 12 weeks – was reached in 61% of patients on abrocitinib at 200 mg/day, 44.5% on 100 mg/day, and 10.4% of controls.
A key secondary endpoint was improvement in itch based on at least a 4-point improvement at week 12 on the Peak Pruritus Numerical Rating Scale from a mean baseline score of 7. This outcome was reached by 55.3% of patients on abrocitinib at 200 mg, 45.2% on 100 mg, and 11.5% on placebo. Of note, the reduction in itch was impressively fast, with significant separation from placebo occurring within the first 24 hours of the study, after just a single dose of abrocitinib. By week 2, roughly one-third of patients on high-dose and one-quarter of those on low-dose abrocitinib had already reached the itch endpoint, the dermatologist continued.
The improvement in pruritus scores in abrocitinib-treated patients was accompanied by significantly greater gains on validated measures of quality of life, another secondary endpoint. The EASI-90 response rate, yet another key secondary outcome, was 37.7% with abrocitinib at 200 mg, 23.9% with 100 mg, and 3.9% with placebo.
The safety profile of abrocitinib was essentially the same as for placebo with the exception of a 3.2% incidence of thrombocytopenia in patients on abrocitinib at 200 mg/day; no cases occurred in controls or patients on abrocitinib at 100 mg/day. Although venous thromboembolism has arisen as a potential concern in clinical trials of oral JAK inhibitors for rheumatoid arthritis, there were no cases in JADE-MONO-2. A long-term safety extension study in JADE-MONO participants is underway.
In an interview, Dr. Gooderham said that, based on the phase 2 study data that’s available for upadacitinib, another JAK-1-selective oral agent, abrocitinib and upadacitinib appear to be in the same ballpark with respect to efficacy as defined by IGA response, EASI improvement, and itch relief.
“The JAK-1 selectivity does seem to offer some advantage in levels of response over more broad JAK inhibition, such as with baritinib,” she added.
Asked how she foresees abrocitinib fitting into clinical practice, should it win regulatory approval for treatment of atopic dermatitis, Dr. Gooderham said it might be considered on a par with the injectable interleukin-4 and -13 inhibitor dupilumab (Dupixent) as next-line therapy after failure on topical therapy or as an option in patients who haven’t responded to or could not tolerate dupilumab. Abrocitinib will be an attractive option for patients who prefer oral therapy and will be an especially appealing medication in patients with a strong itch component to their atopic dermatitis, she added.
The results of JADE COMPARE, a phase 3, head-to-head randomized comparison of abrocitinib and dupilumab, are expected to be presented later this year at the virtual annual congress of the European Academy of Dermatology and Venereology. Pfizer has announced the key results, reporting that the JAK inhibitor at 200 mg/day achieved significantly greater improvements than dupilumab in the coprimary IGA and EASI-75 endpoints at 12 weeks.
JADE-MONO-2 was sponsored by Pfizer. Dr. Gooderham reported receiving research grants from that company and close to two dozen others.
The JADE-MONO-2 results have been published online (JAMA Dermatol. 2020 Jun 3;e201406. doi: 10.1001/jamadermatol.2020.1406).
Melinda Gooderham, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The positive results of this 391-patient, international, randomized, double-blind, placebo-controlled clinical trial mirror those previously reported in the identically designed JADE-MONO-1 pivotal phase 3 trial, noted Dr. Gooderham, medical director of the SKiN Centre for Dermatology and a dermatologist at Queen’s University in Kingston, Ont.
Participants in JADE-MONO-2 were randomized 2:2:1 to abrocitinib at 200 mg once daily, 100 mg once daily, or placebo for 12 weeks. The coprimary endpoint of skin clearance as reflected in an Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with an improvement of at least two grades at week 12 was achieved in 38.1% and 28.4% of patients on 200 and 100 mg of the JAK-1 inhibitor, respectively, compared with 9.1% of placebo-treated controls. The other coprimary endpoint – significant improvement in disease extent as defined by at least a 75% reduction from baseline in Eczema Area and Severity Index (EASI-75 response) at 12 weeks – was reached in 61% of patients on abrocitinib at 200 mg/day, 44.5% on 100 mg/day, and 10.4% of controls.
A key secondary endpoint was improvement in itch based on at least a 4-point improvement at week 12 on the Peak Pruritus Numerical Rating Scale from a mean baseline score of 7. This outcome was reached by 55.3% of patients on abrocitinib at 200 mg, 45.2% on 100 mg, and 11.5% on placebo. Of note, the reduction in itch was impressively fast, with significant separation from placebo occurring within the first 24 hours of the study, after just a single dose of abrocitinib. By week 2, roughly one-third of patients on high-dose and one-quarter of those on low-dose abrocitinib had already reached the itch endpoint, the dermatologist continued.
The improvement in pruritus scores in abrocitinib-treated patients was accompanied by significantly greater gains on validated measures of quality of life, another secondary endpoint. The EASI-90 response rate, yet another key secondary outcome, was 37.7% with abrocitinib at 200 mg, 23.9% with 100 mg, and 3.9% with placebo.
The safety profile of abrocitinib was essentially the same as for placebo with the exception of a 3.2% incidence of thrombocytopenia in patients on abrocitinib at 200 mg/day; no cases occurred in controls or patients on abrocitinib at 100 mg/day. Although venous thromboembolism has arisen as a potential concern in clinical trials of oral JAK inhibitors for rheumatoid arthritis, there were no cases in JADE-MONO-2. A long-term safety extension study in JADE-MONO participants is underway.
In an interview, Dr. Gooderham said that, based on the phase 2 study data that’s available for upadacitinib, another JAK-1-selective oral agent, abrocitinib and upadacitinib appear to be in the same ballpark with respect to efficacy as defined by IGA response, EASI improvement, and itch relief.
“The JAK-1 selectivity does seem to offer some advantage in levels of response over more broad JAK inhibition, such as with baritinib,” she added.
Asked how she foresees abrocitinib fitting into clinical practice, should it win regulatory approval for treatment of atopic dermatitis, Dr. Gooderham said it might be considered on a par with the injectable interleukin-4 and -13 inhibitor dupilumab (Dupixent) as next-line therapy after failure on topical therapy or as an option in patients who haven’t responded to or could not tolerate dupilumab. Abrocitinib will be an attractive option for patients who prefer oral therapy and will be an especially appealing medication in patients with a strong itch component to their atopic dermatitis, she added.
The results of JADE COMPARE, a phase 3, head-to-head randomized comparison of abrocitinib and dupilumab, are expected to be presented later this year at the virtual annual congress of the European Academy of Dermatology and Venereology. Pfizer has announced the key results, reporting that the JAK inhibitor at 200 mg/day achieved significantly greater improvements than dupilumab in the coprimary IGA and EASI-75 endpoints at 12 weeks.
JADE-MONO-2 was sponsored by Pfizer. Dr. Gooderham reported receiving research grants from that company and close to two dozen others.
The JADE-MONO-2 results have been published online (JAMA Dermatol. 2020 Jun 3;e201406. doi: 10.1001/jamadermatol.2020.1406).
Melinda Gooderham, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
The positive results of this 391-patient, international, randomized, double-blind, placebo-controlled clinical trial mirror those previously reported in the identically designed JADE-MONO-1 pivotal phase 3 trial, noted Dr. Gooderham, medical director of the SKiN Centre for Dermatology and a dermatologist at Queen’s University in Kingston, Ont.
Participants in JADE-MONO-2 were randomized 2:2:1 to abrocitinib at 200 mg once daily, 100 mg once daily, or placebo for 12 weeks. The coprimary endpoint of skin clearance as reflected in an Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with an improvement of at least two grades at week 12 was achieved in 38.1% and 28.4% of patients on 200 and 100 mg of the JAK-1 inhibitor, respectively, compared with 9.1% of placebo-treated controls. The other coprimary endpoint – significant improvement in disease extent as defined by at least a 75% reduction from baseline in Eczema Area and Severity Index (EASI-75 response) at 12 weeks – was reached in 61% of patients on abrocitinib at 200 mg/day, 44.5% on 100 mg/day, and 10.4% of controls.
A key secondary endpoint was improvement in itch based on at least a 4-point improvement at week 12 on the Peak Pruritus Numerical Rating Scale from a mean baseline score of 7. This outcome was reached by 55.3% of patients on abrocitinib at 200 mg, 45.2% on 100 mg, and 11.5% on placebo. Of note, the reduction in itch was impressively fast, with significant separation from placebo occurring within the first 24 hours of the study, after just a single dose of abrocitinib. By week 2, roughly one-third of patients on high-dose and one-quarter of those on low-dose abrocitinib had already reached the itch endpoint, the dermatologist continued.
The improvement in pruritus scores in abrocitinib-treated patients was accompanied by significantly greater gains on validated measures of quality of life, another secondary endpoint. The EASI-90 response rate, yet another key secondary outcome, was 37.7% with abrocitinib at 200 mg, 23.9% with 100 mg, and 3.9% with placebo.
The safety profile of abrocitinib was essentially the same as for placebo with the exception of a 3.2% incidence of thrombocytopenia in patients on abrocitinib at 200 mg/day; no cases occurred in controls or patients on abrocitinib at 100 mg/day. Although venous thromboembolism has arisen as a potential concern in clinical trials of oral JAK inhibitors for rheumatoid arthritis, there were no cases in JADE-MONO-2. A long-term safety extension study in JADE-MONO participants is underway.
In an interview, Dr. Gooderham said that, based on the phase 2 study data that’s available for upadacitinib, another JAK-1-selective oral agent, abrocitinib and upadacitinib appear to be in the same ballpark with respect to efficacy as defined by IGA response, EASI improvement, and itch relief.
“The JAK-1 selectivity does seem to offer some advantage in levels of response over more broad JAK inhibition, such as with baritinib,” she added.
Asked how she foresees abrocitinib fitting into clinical practice, should it win regulatory approval for treatment of atopic dermatitis, Dr. Gooderham said it might be considered on a par with the injectable interleukin-4 and -13 inhibitor dupilumab (Dupixent) as next-line therapy after failure on topical therapy or as an option in patients who haven’t responded to or could not tolerate dupilumab. Abrocitinib will be an attractive option for patients who prefer oral therapy and will be an especially appealing medication in patients with a strong itch component to their atopic dermatitis, she added.
The results of JADE COMPARE, a phase 3, head-to-head randomized comparison of abrocitinib and dupilumab, are expected to be presented later this year at the virtual annual congress of the European Academy of Dermatology and Venereology. Pfizer has announced the key results, reporting that the JAK inhibitor at 200 mg/day achieved significantly greater improvements than dupilumab in the coprimary IGA and EASI-75 endpoints at 12 weeks.
JADE-MONO-2 was sponsored by Pfizer. Dr. Gooderham reported receiving research grants from that company and close to two dozen others.
The JADE-MONO-2 results have been published online (JAMA Dermatol. 2020 Jun 3;e201406. doi: 10.1001/jamadermatol.2020.1406).
FROM AAD 20
Adding CGRP to Botox is safe and effective for migraine prevention
Investigators found the CGRP-mAbs significantly reduced the number of headache days and pain severity with adverse event rates similar to those reported in previous trials of these medications.
“The addition of a CGRP monoclonal antibody provided statistically significantly fewer monthly headache days,” said study investigator Fred Cohen, MD, an internal medicine resident physician at Montefiore Health System, New York. “However, this was a retrospective chart review, which is hindered by elements such as recall bias. Therefore, future prospective studies are warranted for higher quality data.”
The findings were presented at the virtual annual meeting of the American Headache Society.
Fewer headache days
Although Botox is associated with significant clinical improvement in chronic migraine, it often fails to adequately control headache frequency and additional medications are needed.
The CGRP-mAbs fremanezumab, galcanezumab, and erenumab, have recently been approved for migraine prevention, with results from clinical trials demonstrating they are effective for both chronic and episodic migraine. However, patients treated with Botox were excluded from these trials and to date there are no data on combination treatment with Botox and CGRP-mAbs.
To determine whether adjunctive treatment with CGRP-mAbs augments Botox therapy in chronic migraine the investigators conducted a retrospective chart review of patients receiving Botox and prescribed a CGRP-mAb.
Eligible patients met the International Classification of Headache Disorders, 3rd edition, criteria for chronic migraine; were age 18 years or older; and presented at a single headache center between May 2018 and May 2019. Patients who received another new therapy during the study or those taking CGRP-mAb treatment for less than 2 months were excluded.
The study’s primary outcome was change in the number of reported monthly headache days, and change in pain severity was the secondary outcome.
The final analysis included data on 153 patients. The population’s mean age was 47.1 years, and 139 patients (90.8%) were women. In all, 89 patients (58.0%) received erenumab (35 received 70 mg and 54 received 140 mg), 51 (33.0%) received galcanezumab, and 13 (9.0%) received fremanezumab.
Overall, 114 (74.5%) patients reported a decrease in monthly headache days or pain severity. In the group of 66 patients for whom quantitative data were available, the average number of monthly headache days before Botox treatment was 25.7. After Botox treatment, patients had an average decrease of 10.9 monthly headache days, a 42.4% reduction, so on average study participants continued to have an average of 14.8 monthly headache days.
After treatment with a CGRP-mAb the number decreased by 5.6 additional days (37.8%). Patients receiving combined therapy had an average of 9.1 monthly headache days. The total decrease from baseline was 16.6 fewer monthly headache days, a 64.6% reduction.
The number of headache days per month was reduced to 9.3 for erenumab and galcanezumab and 5.8 for fremanezumab. However, few patients in the study took fremanezumab so this result had less statistical power than the results for the other CGRP-mAbs.
A total of 13 patients (8.5%) reported side effects associated with the CGRP-mAbs, which included constipation, injection-site reaction, and fatigue.
More evidence is needed
Commenting on the findings, Peter McAllister, MD, medical director of the New England Institute for Neurology and Headache in Stamford, Conn., said the study’s main limitation is that it is a retrospective chart review, which yields lower level evidence than a prospective, double-blind, placebo-controlled study. Dr. McAllister, who was not involved in the research, also noted that the sample size was small, particularly with respect to fremanezumab.
“This study, despite its limitations, shows that addition of a monoclonal antibody to onabotulinumtoxinA is safe and well tolerated, and may confer additional reduction in migraine or headache days. The authors correctly state that more evidence via prospective study is warranted,” said Dr. McAllister, who is also chief medical officer of the New England Institute for Clinical Research and was not involved in the investigation.
Dr. Cohen has reported no relevant financial relationships. Dr. McAllister was an investigator in the PREEMPT trial of onabotulinumtoxinA, as well as in all of the phase 3 monoclonal antibody studies.
A version of this article originally appeared on Medscape.com.
Investigators found the CGRP-mAbs significantly reduced the number of headache days and pain severity with adverse event rates similar to those reported in previous trials of these medications.
“The addition of a CGRP monoclonal antibody provided statistically significantly fewer monthly headache days,” said study investigator Fred Cohen, MD, an internal medicine resident physician at Montefiore Health System, New York. “However, this was a retrospective chart review, which is hindered by elements such as recall bias. Therefore, future prospective studies are warranted for higher quality data.”
The findings were presented at the virtual annual meeting of the American Headache Society.
Fewer headache days
Although Botox is associated with significant clinical improvement in chronic migraine, it often fails to adequately control headache frequency and additional medications are needed.
The CGRP-mAbs fremanezumab, galcanezumab, and erenumab, have recently been approved for migraine prevention, with results from clinical trials demonstrating they are effective for both chronic and episodic migraine. However, patients treated with Botox were excluded from these trials and to date there are no data on combination treatment with Botox and CGRP-mAbs.
To determine whether adjunctive treatment with CGRP-mAbs augments Botox therapy in chronic migraine the investigators conducted a retrospective chart review of patients receiving Botox and prescribed a CGRP-mAb.
Eligible patients met the International Classification of Headache Disorders, 3rd edition, criteria for chronic migraine; were age 18 years or older; and presented at a single headache center between May 2018 and May 2019. Patients who received another new therapy during the study or those taking CGRP-mAb treatment for less than 2 months were excluded.
The study’s primary outcome was change in the number of reported monthly headache days, and change in pain severity was the secondary outcome.
The final analysis included data on 153 patients. The population’s mean age was 47.1 years, and 139 patients (90.8%) were women. In all, 89 patients (58.0%) received erenumab (35 received 70 mg and 54 received 140 mg), 51 (33.0%) received galcanezumab, and 13 (9.0%) received fremanezumab.
Overall, 114 (74.5%) patients reported a decrease in monthly headache days or pain severity. In the group of 66 patients for whom quantitative data were available, the average number of monthly headache days before Botox treatment was 25.7. After Botox treatment, patients had an average decrease of 10.9 monthly headache days, a 42.4% reduction, so on average study participants continued to have an average of 14.8 monthly headache days.
After treatment with a CGRP-mAb the number decreased by 5.6 additional days (37.8%). Patients receiving combined therapy had an average of 9.1 monthly headache days. The total decrease from baseline was 16.6 fewer monthly headache days, a 64.6% reduction.
The number of headache days per month was reduced to 9.3 for erenumab and galcanezumab and 5.8 for fremanezumab. However, few patients in the study took fremanezumab so this result had less statistical power than the results for the other CGRP-mAbs.
A total of 13 patients (8.5%) reported side effects associated with the CGRP-mAbs, which included constipation, injection-site reaction, and fatigue.
More evidence is needed
Commenting on the findings, Peter McAllister, MD, medical director of the New England Institute for Neurology and Headache in Stamford, Conn., said the study’s main limitation is that it is a retrospective chart review, which yields lower level evidence than a prospective, double-blind, placebo-controlled study. Dr. McAllister, who was not involved in the research, also noted that the sample size was small, particularly with respect to fremanezumab.
“This study, despite its limitations, shows that addition of a monoclonal antibody to onabotulinumtoxinA is safe and well tolerated, and may confer additional reduction in migraine or headache days. The authors correctly state that more evidence via prospective study is warranted,” said Dr. McAllister, who is also chief medical officer of the New England Institute for Clinical Research and was not involved in the investigation.
Dr. Cohen has reported no relevant financial relationships. Dr. McAllister was an investigator in the PREEMPT trial of onabotulinumtoxinA, as well as in all of the phase 3 monoclonal antibody studies.
A version of this article originally appeared on Medscape.com.
Investigators found the CGRP-mAbs significantly reduced the number of headache days and pain severity with adverse event rates similar to those reported in previous trials of these medications.
“The addition of a CGRP monoclonal antibody provided statistically significantly fewer monthly headache days,” said study investigator Fred Cohen, MD, an internal medicine resident physician at Montefiore Health System, New York. “However, this was a retrospective chart review, which is hindered by elements such as recall bias. Therefore, future prospective studies are warranted for higher quality data.”
The findings were presented at the virtual annual meeting of the American Headache Society.
Fewer headache days
Although Botox is associated with significant clinical improvement in chronic migraine, it often fails to adequately control headache frequency and additional medications are needed.
The CGRP-mAbs fremanezumab, galcanezumab, and erenumab, have recently been approved for migraine prevention, with results from clinical trials demonstrating they are effective for both chronic and episodic migraine. However, patients treated with Botox were excluded from these trials and to date there are no data on combination treatment with Botox and CGRP-mAbs.
To determine whether adjunctive treatment with CGRP-mAbs augments Botox therapy in chronic migraine the investigators conducted a retrospective chart review of patients receiving Botox and prescribed a CGRP-mAb.
Eligible patients met the International Classification of Headache Disorders, 3rd edition, criteria for chronic migraine; were age 18 years or older; and presented at a single headache center between May 2018 and May 2019. Patients who received another new therapy during the study or those taking CGRP-mAb treatment for less than 2 months were excluded.
The study’s primary outcome was change in the number of reported monthly headache days, and change in pain severity was the secondary outcome.
The final analysis included data on 153 patients. The population’s mean age was 47.1 years, and 139 patients (90.8%) were women. In all, 89 patients (58.0%) received erenumab (35 received 70 mg and 54 received 140 mg), 51 (33.0%) received galcanezumab, and 13 (9.0%) received fremanezumab.
Overall, 114 (74.5%) patients reported a decrease in monthly headache days or pain severity. In the group of 66 patients for whom quantitative data were available, the average number of monthly headache days before Botox treatment was 25.7. After Botox treatment, patients had an average decrease of 10.9 monthly headache days, a 42.4% reduction, so on average study participants continued to have an average of 14.8 monthly headache days.
After treatment with a CGRP-mAb the number decreased by 5.6 additional days (37.8%). Patients receiving combined therapy had an average of 9.1 monthly headache days. The total decrease from baseline was 16.6 fewer monthly headache days, a 64.6% reduction.
The number of headache days per month was reduced to 9.3 for erenumab and galcanezumab and 5.8 for fremanezumab. However, few patients in the study took fremanezumab so this result had less statistical power than the results for the other CGRP-mAbs.
A total of 13 patients (8.5%) reported side effects associated with the CGRP-mAbs, which included constipation, injection-site reaction, and fatigue.
More evidence is needed
Commenting on the findings, Peter McAllister, MD, medical director of the New England Institute for Neurology and Headache in Stamford, Conn., said the study’s main limitation is that it is a retrospective chart review, which yields lower level evidence than a prospective, double-blind, placebo-controlled study. Dr. McAllister, who was not involved in the research, also noted that the sample size was small, particularly with respect to fremanezumab.
“This study, despite its limitations, shows that addition of a monoclonal antibody to onabotulinumtoxinA is safe and well tolerated, and may confer additional reduction in migraine or headache days. The authors correctly state that more evidence via prospective study is warranted,” said Dr. McAllister, who is also chief medical officer of the New England Institute for Clinical Research and was not involved in the investigation.
Dr. Cohen has reported no relevant financial relationships. Dr. McAllister was an investigator in the PREEMPT trial of onabotulinumtoxinA, as well as in all of the phase 3 monoclonal antibody studies.
A version of this article originally appeared on Medscape.com.
FROM AHS 2020
Minority-serving hospitals had similar survival after liver cancer surgery
Overall survival after liver cancer surgery was similar regardless of whether patients were treated at minority-serving hospitals or at hospitals with proportionally fewer African American or Hispanic patients, investigators have found.
“[T]reatment of racial minorities is largely restricted to a subset of hospitals, often referred to as minority-serving hospitals. We sought to examine whether racial and ethnic minorities with hepatocellular carcinoma receive their surgical care at minority-serving hospitals, and whether treatment at minority-serving hospitals is associated with differences in overall survival,” explained Winta T. Mehtsun, MD, MPH, of Dana-Farber Cancer Institute in Boston and associates in an abstract released as part of the annual Digestive Disease Week.®
Hepatocellular carcinoma continues to have a low 5-year survival rate and exhibits marked racial and ethnic disparities in diagnosis, treatment, and outcomes. In a recent study of Surveillance Epidemiology and End Results (SEER) data, African American patients with hepatocellular carcinoma were significantly younger at diagnosis, were more likely to have metastatic disease, and were less likely to receive surgical treatment compared with whites (Am J Prevent Med 2018;55:S40-48). Among patients with early-stage liver cancer, Hispanic and African American patients are less likely to receive curative therapy and die sooner, on average, than do other patients (Clin Gastroenterol Hepatol. 2019;17:551-9).
Minority-serving hospitals also have improved significantly less over time on measures of critical care, length of stay, and mortality, but whether these issues extend to hepatocellular carcinoma remains unclear. Therefore, Dr. Mehtsun and her associates studied all 2,609 patients in the National Cancer Database who received surgical resection (not transplantation or local therapy) for nonmetastatic hepatocellular carcinoma between 2004 and 2014. They compared survival at minority-serving hospitals – those in the top 10% based on the proportion of patients who were African American or Hispanic – with survival at other hospitals.
“There was no association between minority-serving hospital and overall survival,” the researchers reported (multivariable hazard ratio for death, 0.89; 95% confidence interval, 0.72-1.11). In contrast, survival was significantly shorter among patients with more advanced disease (HR, 2.5; 95% CI, 2.1-2.8), patients who were treated at a community cancer program (HR, 1.7; 95% CI, 1.3-2.4), and patients whose Charlson Comorbidity Index was greater than 2 (HR, 1.2; 95% CI, 1.1-1.4).
Stage at diagnosis, comorbidities, and sex were not significantly related to hospital type, the investigators noted. A total of 298 patients (11%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were significantly more likely to be uninsured (11% vs. 4% at other hospitals) and significantly less likely to be treated at an academic center (55% vs. 69%; both P less than .001).
Dr. Mehtsun reported having no relevant conflicts of interest.
SOURCE: Mehtsun WT et al. DDW 2020, Abstract Tu2043.
Overall survival after liver cancer surgery was similar regardless of whether patients were treated at minority-serving hospitals or at hospitals with proportionally fewer African American or Hispanic patients, investigators have found.
“[T]reatment of racial minorities is largely restricted to a subset of hospitals, often referred to as minority-serving hospitals. We sought to examine whether racial and ethnic minorities with hepatocellular carcinoma receive their surgical care at minority-serving hospitals, and whether treatment at minority-serving hospitals is associated with differences in overall survival,” explained Winta T. Mehtsun, MD, MPH, of Dana-Farber Cancer Institute in Boston and associates in an abstract released as part of the annual Digestive Disease Week.®
Hepatocellular carcinoma continues to have a low 5-year survival rate and exhibits marked racial and ethnic disparities in diagnosis, treatment, and outcomes. In a recent study of Surveillance Epidemiology and End Results (SEER) data, African American patients with hepatocellular carcinoma were significantly younger at diagnosis, were more likely to have metastatic disease, and were less likely to receive surgical treatment compared with whites (Am J Prevent Med 2018;55:S40-48). Among patients with early-stage liver cancer, Hispanic and African American patients are less likely to receive curative therapy and die sooner, on average, than do other patients (Clin Gastroenterol Hepatol. 2019;17:551-9).
Minority-serving hospitals also have improved significantly less over time on measures of critical care, length of stay, and mortality, but whether these issues extend to hepatocellular carcinoma remains unclear. Therefore, Dr. Mehtsun and her associates studied all 2,609 patients in the National Cancer Database who received surgical resection (not transplantation or local therapy) for nonmetastatic hepatocellular carcinoma between 2004 and 2014. They compared survival at minority-serving hospitals – those in the top 10% based on the proportion of patients who were African American or Hispanic – with survival at other hospitals.
“There was no association between minority-serving hospital and overall survival,” the researchers reported (multivariable hazard ratio for death, 0.89; 95% confidence interval, 0.72-1.11). In contrast, survival was significantly shorter among patients with more advanced disease (HR, 2.5; 95% CI, 2.1-2.8), patients who were treated at a community cancer program (HR, 1.7; 95% CI, 1.3-2.4), and patients whose Charlson Comorbidity Index was greater than 2 (HR, 1.2; 95% CI, 1.1-1.4).
Stage at diagnosis, comorbidities, and sex were not significantly related to hospital type, the investigators noted. A total of 298 patients (11%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were significantly more likely to be uninsured (11% vs. 4% at other hospitals) and significantly less likely to be treated at an academic center (55% vs. 69%; both P less than .001).
Dr. Mehtsun reported having no relevant conflicts of interest.
SOURCE: Mehtsun WT et al. DDW 2020, Abstract Tu2043.
Overall survival after liver cancer surgery was similar regardless of whether patients were treated at minority-serving hospitals or at hospitals with proportionally fewer African American or Hispanic patients, investigators have found.
“[T]reatment of racial minorities is largely restricted to a subset of hospitals, often referred to as minority-serving hospitals. We sought to examine whether racial and ethnic minorities with hepatocellular carcinoma receive their surgical care at minority-serving hospitals, and whether treatment at minority-serving hospitals is associated with differences in overall survival,” explained Winta T. Mehtsun, MD, MPH, of Dana-Farber Cancer Institute in Boston and associates in an abstract released as part of the annual Digestive Disease Week.®
Hepatocellular carcinoma continues to have a low 5-year survival rate and exhibits marked racial and ethnic disparities in diagnosis, treatment, and outcomes. In a recent study of Surveillance Epidemiology and End Results (SEER) data, African American patients with hepatocellular carcinoma were significantly younger at diagnosis, were more likely to have metastatic disease, and were less likely to receive surgical treatment compared with whites (Am J Prevent Med 2018;55:S40-48). Among patients with early-stage liver cancer, Hispanic and African American patients are less likely to receive curative therapy and die sooner, on average, than do other patients (Clin Gastroenterol Hepatol. 2019;17:551-9).
Minority-serving hospitals also have improved significantly less over time on measures of critical care, length of stay, and mortality, but whether these issues extend to hepatocellular carcinoma remains unclear. Therefore, Dr. Mehtsun and her associates studied all 2,609 patients in the National Cancer Database who received surgical resection (not transplantation or local therapy) for nonmetastatic hepatocellular carcinoma between 2004 and 2014. They compared survival at minority-serving hospitals – those in the top 10% based on the proportion of patients who were African American or Hispanic – with survival at other hospitals.
“There was no association between minority-serving hospital and overall survival,” the researchers reported (multivariable hazard ratio for death, 0.89; 95% confidence interval, 0.72-1.11). In contrast, survival was significantly shorter among patients with more advanced disease (HR, 2.5; 95% CI, 2.1-2.8), patients who were treated at a community cancer program (HR, 1.7; 95% CI, 1.3-2.4), and patients whose Charlson Comorbidity Index was greater than 2 (HR, 1.2; 95% CI, 1.1-1.4).
Stage at diagnosis, comorbidities, and sex were not significantly related to hospital type, the investigators noted. A total of 298 patients (11%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were significantly more likely to be uninsured (11% vs. 4% at other hospitals) and significantly less likely to be treated at an academic center (55% vs. 69%; both P less than .001).
Dr. Mehtsun reported having no relevant conflicts of interest.
SOURCE: Mehtsun WT et al. DDW 2020, Abstract Tu2043.
FROM DDW 2020