Conference Coverage

Mounting evidence confirms what many clinicians have suspected for years: That daily moisturizers are the bedrock of atopic dermatitis management.

In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.

Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:

1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.

2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.

3. It promotes a healthy microbiome via induction of antimicrobial peptides.

4. It maintains stratum corneum acidification, which protects against pathogens.

5. It reduces recurrence of flares when used daily.

6. It prevents the onset of AD when applied early in life to at-risk children.

A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”

In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.

“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”

With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”

Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”

A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”

She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.

dbrunk@mdedge.com

Mounting evidence confirms what many clinicians have suspected for years: That daily moisturizers are the bedrock of atopic dermatitis management.

In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.

Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:

1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.

2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.

3. It promotes a healthy microbiome via induction of antimicrobial peptides.

4. It maintains stratum corneum acidification, which protects against pathogens.

5. It reduces recurrence of flares when used daily.

6. It prevents the onset of AD when applied early in life to at-risk children.

A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”

In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.

“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”

With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”

Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”

A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”

She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.

dbrunk@mdedge.com

Mounting evidence confirms what many clinicians have suspected for years: That daily moisturizers are the bedrock of atopic dermatitis management.

In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.

Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:

1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.

2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.

3. It promotes a healthy microbiome via induction of antimicrobial peptides.

4. It maintains stratum corneum acidification, which protects against pathogens.

5. It reduces recurrence of flares when used daily.

6. It prevents the onset of AD when applied early in life to at-risk children.

A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”

In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.

“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”

With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”

Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”

A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”

She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.

dbrunk@mdedge.com

Combining an EGFR inhibitor with a pair of checkpoint inhibitors can produce “promising” activity in certain patients with colorectal cancer (CRC), according to an investigator from a phase 2 trial.

The trial was designed to test the combination of panitumumab, ipilimumab, and nivolumab in patients with previously treated, unresectable and/or metastatic, microsatellite stable or mismatch repair–proficient CRC without mutations in KRAS, NRAS, or BRAF.

Among 49 evaluable patients treated with the triplet, 35% had a partial response at 12 weeks of follow-up, which met the trial’s primary response endpoint, according to investigator Michael S. Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“Though toxicities were, of course, observed, they were consistent overall with the expected adverse event profiles of anti-EGFR therapy and combination ipilimumab and nivolumab. Correlative studies are ongoing to identify potential biomarkers of response,” Dr. Lee said when presenting the trial results at the 2021 Gastrointestinal Cancers Symposium (Abstract 7).

Immune activation?

The rationale for adding panitumumab to immune checkpoint inhibitors comes, in part, from a trial published in 2014 in The Lancet Oncology. The trial showed that panitumumab was noninferior to cetuximab. Panitumumab was associated with a 22% response rate in patients with KRAS wild-type, metastatic CRC that was refractory to chemotherapy. Progression-free survival (PFS) and overall survival (OS) were similar between the treatment arms.

In addition, in mouse models of RAS wild-type CRC, treatment with an anti-EGFR antibody induced immunogenic cell death.

“Moreover, translational studies of tumor biopsies from patients who were treated with the anti-EGFR antibody cetuximab showed that responders had significant increases in T-cell infiltration and cytolytic activity within tumors after starting treatment,” Dr. Lee said.

In the latter studies, tumor samples taken at the time of disease progression also showed increased expression of immune checkpoint inhibitor pathways, including PD-L1, the primary target of nivolumab, and CTLA-4, the primary target of ipilimumab.

“Given this, we hypothesized that combining anti–PD-1 and anti–CTLA-4 antibodies with anti-EGFR therapy would be synergistic,” Dr. Lee said.

Single-arm study

Investigators enrolled patients with unresectable and/or metastatic CRC in the trial. All patients had disease that was KRAS, NRAS, and BRAF wild-type, and they had either microsatellite stability or proficient mismatch repair. Patients also had to have received one or two prior lines of therapy, not including an anti-EGFR agent.

The patients received panitumumab at 6 mg/kg IV every 2 weeks, nivolumab at 240 mg IV every 2 weeks, and ipilimumab at 1 mg/kg IV every 6 weeks.

Of all 56 patients enrolled, 28 (50%) had tumors in the left colon, 3 (5%) had tumors in the right colon, 2 (4%) had tumors in the transverse colon, 16 (29%) had rectal tumors, and 7 (13%) were not specified.

As noted before, 49 patients were evaluable, and the trial met its primary endpoint of responses in at least 17 patients (35%) at 12 weeks. All were partial responses.

Of the remaining patients, 21 (43%) had stable disease, and 11 (22%) had disease progression. Of the latter group, five patients did not have documented radiographic progression at 12 weeks, but they discontinued therapy before restaging because of unequivocal clinical progression.

The best response rate (confirmed and unconfirmed) at any time was 41%.

At a median follow-up of 12.1 months, the median PFS was 5.7 months. The OS data were not mature at the time of data cutoff. However, the median OS was 27 months.

There were two deaths on study, one from myocarditis possibly related to the study treatment, and one from colonic perforation, which was deemed unlikely to be treatment related.

Grade 3 or 4 adverse events included hypomagnesemia (n = 6), acneiform rash (n = 6), increased lipase (n = 5), increased amylase (n = 4), alanine aminotransferase elevation (n = 3), aspartate aminotransferase elevation (n = 3), diarrhea (n = 3), hyophosphatemia (n = 3), and maculopapular rash (n = 3).

‘Disappointing PFS’

In the question and answer session following the presentation, moderator Michael J. Hall, MD, of Fox Chase Cancer Center in Philadelphia, asked whether the response rate seen with the addition of panitumumab was what the investigators expected, independent of the dual–checkpoint inhibitor therapy, and “with the relatively disappointing PFS you saw, what are the plans moving forward with this regimen?”

“These are great questions and thoughts I’ve had as well,” Dr. Lee replied.

He noted that studies of other anti-EGFR and checkpoint inhibitor combinations have had relatively low response rates, and his group’s study was conducted with “an effort to try and get over this immune-cold environment that we know exists in the tumor microenvironment,” he said.

Dr. Lee also acknowledged that the response rate may have been slightly higher than that seen in other studies because of the preponderance of left colon tumors, which are generally more amenable to systemic therapy.

Regarding PFS, Dr. Lee said the analyses of durability of response are still ongoing, and the median PFS was better than that seen in a trial of single-agent panitumumab in a similar population.

The current study was funded by Amgen and Bristol Myers Squibb. Dr. Lee disclosed institutional research funding from the companies, consulting/advising for Pfizer, and travel expenses from Genentech/Roche. Dr. Hall disclosed relationships with Ambry Genetics, AstraZeneca, Caris Life Sciences, Foundation Medicine, InVitae, and Myriad Genetics. He also shares a patent with several Fox Chase investigators for a novel method to investigate hereditary CRC genes.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Combining an EGFR inhibitor with a pair of checkpoint inhibitors can produce “promising” activity in certain patients with colorectal cancer (CRC), according to an investigator from a phase 2 trial.

The trial was designed to test the combination of panitumumab, ipilimumab, and nivolumab in patients with previously treated, unresectable and/or metastatic, microsatellite stable or mismatch repair–proficient CRC without mutations in KRAS, NRAS, or BRAF.

Among 49 evaluable patients treated with the triplet, 35% had a partial response at 12 weeks of follow-up, which met the trial’s primary response endpoint, according to investigator Michael S. Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“Though toxicities were, of course, observed, they were consistent overall with the expected adverse event profiles of anti-EGFR therapy and combination ipilimumab and nivolumab. Correlative studies are ongoing to identify potential biomarkers of response,” Dr. Lee said when presenting the trial results at the 2021 Gastrointestinal Cancers Symposium (Abstract 7).

Immune activation?

The rationale for adding panitumumab to immune checkpoint inhibitors comes, in part, from a trial published in 2014 in The Lancet Oncology. The trial showed that panitumumab was noninferior to cetuximab. Panitumumab was associated with a 22% response rate in patients with KRAS wild-type, metastatic CRC that was refractory to chemotherapy. Progression-free survival (PFS) and overall survival (OS) were similar between the treatment arms.

In addition, in mouse models of RAS wild-type CRC, treatment with an anti-EGFR antibody induced immunogenic cell death.

“Moreover, translational studies of tumor biopsies from patients who were treated with the anti-EGFR antibody cetuximab showed that responders had significant increases in T-cell infiltration and cytolytic activity within tumors after starting treatment,” Dr. Lee said.

In the latter studies, tumor samples taken at the time of disease progression also showed increased expression of immune checkpoint inhibitor pathways, including PD-L1, the primary target of nivolumab, and CTLA-4, the primary target of ipilimumab.

“Given this, we hypothesized that combining anti–PD-1 and anti–CTLA-4 antibodies with anti-EGFR therapy would be synergistic,” Dr. Lee said.

Single-arm study

Investigators enrolled patients with unresectable and/or metastatic CRC in the trial. All patients had disease that was KRAS, NRAS, and BRAF wild-type, and they had either microsatellite stability or proficient mismatch repair. Patients also had to have received one or two prior lines of therapy, not including an anti-EGFR agent.

The patients received panitumumab at 6 mg/kg IV every 2 weeks, nivolumab at 240 mg IV every 2 weeks, and ipilimumab at 1 mg/kg IV every 6 weeks.

Of all 56 patients enrolled, 28 (50%) had tumors in the left colon, 3 (5%) had tumors in the right colon, 2 (4%) had tumors in the transverse colon, 16 (29%) had rectal tumors, and 7 (13%) were not specified.

As noted before, 49 patients were evaluable, and the trial met its primary endpoint of responses in at least 17 patients (35%) at 12 weeks. All were partial responses.

Of the remaining patients, 21 (43%) had stable disease, and 11 (22%) had disease progression. Of the latter group, five patients did not have documented radiographic progression at 12 weeks, but they discontinued therapy before restaging because of unequivocal clinical progression.

The best response rate (confirmed and unconfirmed) at any time was 41%.

At a median follow-up of 12.1 months, the median PFS was 5.7 months. The OS data were not mature at the time of data cutoff. However, the median OS was 27 months.

There were two deaths on study, one from myocarditis possibly related to the study treatment, and one from colonic perforation, which was deemed unlikely to be treatment related.

Grade 3 or 4 adverse events included hypomagnesemia (n = 6), acneiform rash (n = 6), increased lipase (n = 5), increased amylase (n = 4), alanine aminotransferase elevation (n = 3), aspartate aminotransferase elevation (n = 3), diarrhea (n = 3), hyophosphatemia (n = 3), and maculopapular rash (n = 3).

‘Disappointing PFS’

In the question and answer session following the presentation, moderator Michael J. Hall, MD, of Fox Chase Cancer Center in Philadelphia, asked whether the response rate seen with the addition of panitumumab was what the investigators expected, independent of the dual–checkpoint inhibitor therapy, and “with the relatively disappointing PFS you saw, what are the plans moving forward with this regimen?”

“These are great questions and thoughts I’ve had as well,” Dr. Lee replied.

He noted that studies of other anti-EGFR and checkpoint inhibitor combinations have had relatively low response rates, and his group’s study was conducted with “an effort to try and get over this immune-cold environment that we know exists in the tumor microenvironment,” he said.

Dr. Lee also acknowledged that the response rate may have been slightly higher than that seen in other studies because of the preponderance of left colon tumors, which are generally more amenable to systemic therapy.

Regarding PFS, Dr. Lee said the analyses of durability of response are still ongoing, and the median PFS was better than that seen in a trial of single-agent panitumumab in a similar population.

The current study was funded by Amgen and Bristol Myers Squibb. Dr. Lee disclosed institutional research funding from the companies, consulting/advising for Pfizer, and travel expenses from Genentech/Roche. Dr. Hall disclosed relationships with Ambry Genetics, AstraZeneca, Caris Life Sciences, Foundation Medicine, InVitae, and Myriad Genetics. He also shares a patent with several Fox Chase investigators for a novel method to investigate hereditary CRC genes.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Combining an EGFR inhibitor with a pair of checkpoint inhibitors can produce “promising” activity in certain patients with colorectal cancer (CRC), according to an investigator from a phase 2 trial.

The trial was designed to test the combination of panitumumab, ipilimumab, and nivolumab in patients with previously treated, unresectable and/or metastatic, microsatellite stable or mismatch repair–proficient CRC without mutations in KRAS, NRAS, or BRAF.

Among 49 evaluable patients treated with the triplet, 35% had a partial response at 12 weeks of follow-up, which met the trial’s primary response endpoint, according to investigator Michael S. Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“Though toxicities were, of course, observed, they were consistent overall with the expected adverse event profiles of anti-EGFR therapy and combination ipilimumab and nivolumab. Correlative studies are ongoing to identify potential biomarkers of response,” Dr. Lee said when presenting the trial results at the 2021 Gastrointestinal Cancers Symposium (Abstract 7).

Immune activation?

The rationale for adding panitumumab to immune checkpoint inhibitors comes, in part, from a trial published in 2014 in The Lancet Oncology. The trial showed that panitumumab was noninferior to cetuximab. Panitumumab was associated with a 22% response rate in patients with KRAS wild-type, metastatic CRC that was refractory to chemotherapy. Progression-free survival (PFS) and overall survival (OS) were similar between the treatment arms.

In addition, in mouse models of RAS wild-type CRC, treatment with an anti-EGFR antibody induced immunogenic cell death.

“Moreover, translational studies of tumor biopsies from patients who were treated with the anti-EGFR antibody cetuximab showed that responders had significant increases in T-cell infiltration and cytolytic activity within tumors after starting treatment,” Dr. Lee said.

In the latter studies, tumor samples taken at the time of disease progression also showed increased expression of immune checkpoint inhibitor pathways, including PD-L1, the primary target of nivolumab, and CTLA-4, the primary target of ipilimumab.

“Given this, we hypothesized that combining anti–PD-1 and anti–CTLA-4 antibodies with anti-EGFR therapy would be synergistic,” Dr. Lee said.

Single-arm study

Investigators enrolled patients with unresectable and/or metastatic CRC in the trial. All patients had disease that was KRAS, NRAS, and BRAF wild-type, and they had either microsatellite stability or proficient mismatch repair. Patients also had to have received one or two prior lines of therapy, not including an anti-EGFR agent.

The patients received panitumumab at 6 mg/kg IV every 2 weeks, nivolumab at 240 mg IV every 2 weeks, and ipilimumab at 1 mg/kg IV every 6 weeks.

Of all 56 patients enrolled, 28 (50%) had tumors in the left colon, 3 (5%) had tumors in the right colon, 2 (4%) had tumors in the transverse colon, 16 (29%) had rectal tumors, and 7 (13%) were not specified.

As noted before, 49 patients were evaluable, and the trial met its primary endpoint of responses in at least 17 patients (35%) at 12 weeks. All were partial responses.

Of the remaining patients, 21 (43%) had stable disease, and 11 (22%) had disease progression. Of the latter group, five patients did not have documented radiographic progression at 12 weeks, but they discontinued therapy before restaging because of unequivocal clinical progression.

The best response rate (confirmed and unconfirmed) at any time was 41%.

At a median follow-up of 12.1 months, the median PFS was 5.7 months. The OS data were not mature at the time of data cutoff. However, the median OS was 27 months.

There were two deaths on study, one from myocarditis possibly related to the study treatment, and one from colonic perforation, which was deemed unlikely to be treatment related.

Grade 3 or 4 adverse events included hypomagnesemia (n = 6), acneiform rash (n = 6), increased lipase (n = 5), increased amylase (n = 4), alanine aminotransferase elevation (n = 3), aspartate aminotransferase elevation (n = 3), diarrhea (n = 3), hyophosphatemia (n = 3), and maculopapular rash (n = 3).

‘Disappointing PFS’

In the question and answer session following the presentation, moderator Michael J. Hall, MD, of Fox Chase Cancer Center in Philadelphia, asked whether the response rate seen with the addition of panitumumab was what the investigators expected, independent of the dual–checkpoint inhibitor therapy, and “with the relatively disappointing PFS you saw, what are the plans moving forward with this regimen?”

“These are great questions and thoughts I’ve had as well,” Dr. Lee replied.

He noted that studies of other anti-EGFR and checkpoint inhibitor combinations have had relatively low response rates, and his group’s study was conducted with “an effort to try and get over this immune-cold environment that we know exists in the tumor microenvironment,” he said.

Dr. Lee also acknowledged that the response rate may have been slightly higher than that seen in other studies because of the preponderance of left colon tumors, which are generally more amenable to systemic therapy.

Regarding PFS, Dr. Lee said the analyses of durability of response are still ongoing, and the median PFS was better than that seen in a trial of single-agent panitumumab in a similar population.

The current study was funded by Amgen and Bristol Myers Squibb. Dr. Lee disclosed institutional research funding from the companies, consulting/advising for Pfizer, and travel expenses from Genentech/Roche. Dr. Hall disclosed relationships with Ambry Genetics, AstraZeneca, Caris Life Sciences, Foundation Medicine, InVitae, and Myriad Genetics. He also shares a patent with several Fox Chase investigators for a novel method to investigate hereditary CRC genes.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A novel blood test has shown promise for colorectal cancer screening.

The “multiomics” test, under development by Freenome, has previously been shown to detect early-stage (I/II) colorectal cancer with a sensitivity of 94% and a specificity of 94%.

A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (AAs).

“The ability to detect advanced adenomas is incredibly important because we can remove them before they become cancerous,” senior author Aasma Shaukat, MD, MPH, chief of gastroenterology at Minneapolis VA Health Care System and professor of medicine at the University of Minnesota, Minneapolis, said in a statement.

At the Gastrointestinal Cancers Symposium 2021, she presented data showing that the novel test was able to detect AAs with a sensitivity of 41% and a specificity of 90%.

This sensitivity of the new test is better than or similar to that of currently available stool tests, noted study author C. Jimmy Lin, MD, PhD, MHS, chief scientific officer at Freenome.

The new test had almost double the sensitivity for detecting AAs (41% vs. 24%) as the fecal immunochemical test (FIT), and its sensitivity was comparable to that of FIT-DNA testing (41% vs. 42%).

In addition, it showed much higher sensitivity (41% vs 22%) for detecting AAs than the Epi proColon, a screening blood test that has been approved by the U.S. Food and Drug Administration for detecting methylated septin 9 DNA (mSEPT9).

“What’s special about our company is ... that we use a multinomic technology, meaning we look at DNA, RNA, protein, and other biomarkers – all of these things together,” Dr. Lin told this news organization.

Their platform integrates assays for circulating free DNA, methylation, and proteins using advanced computational biology and machine-learning techniques, which provide a multidimensional view of both tumor- and immune-derived signatures that enable the early detection of cancer.

In contrast to other blood tests that are under development for cancer screening, some of which claim to detect several common cancer types, Freenome is focusing on only colorectal cancer. “There are other companies in the early-detection space, but some of them are doing multicancer screening and have a generalized product,” said Dr. Lin. “Our approach is to focus on a specific cancer type, and we are beginning with colorectal cancer screening, and then will expand to other types.”
 

Better sensitivity

The study that was presented at the meeting evaluated the novel multiomics blood test for AA detection.

Blood samples were obtained from participants in the AI-EMERGE study, a prospective, multicenter study that included primarily average-risk screening patients from 30 clinical sites in the United States and Canada. The study included a total of 542 samples, including 122 histopathologically confirmed AAs and 420 colonoscopy-confirmed negative control samples.

AA sensitivity of the novel test was greater than that with the mSEPT9 test, which is the only blood test currently available for colorectal cancer screening. The new test’s sensitivity was much higher than that of FIT and was comparable to that of FIT-DNA. Sensitivity increased with increasing lesion size and was consistent across location and histology except for serrated lesions, the authors noted in the abstract.

“By combining signatures from both tumor and non–tumor-derived sources, our multiomics signatures detect twice as many AAs as methylation only or single-protein approaches,” Dr. Lin said. “And we have now shown that sensitive AA detection at a level similar to or better than currently available stool tests is achievable in blood, which is necessary for effective early detection and prevention of colorectal cancers.”

The company has begun the regulatory process for having the test approved by the FDA. The company’s goal is to enroll 14,000 participants and have prospectively collected data.

The research was funded by Freenome. Dr. Lin is the chief scientific officer at Freenome and has relationships with Labroots, Natera, and Neon Therapeutics. Dr. Shaukat has relationships with Freenome and Iterative Scopes.

This article was updated 2/2/21.

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

A novel blood test has shown promise for colorectal cancer screening.

The “multiomics” test, under development by Freenome, has previously been shown to detect early-stage (I/II) colorectal cancer with a sensitivity of 94% and a specificity of 94%.

A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (AAs).

“The ability to detect advanced adenomas is incredibly important because we can remove them before they become cancerous,” senior author Aasma Shaukat, MD, MPH, chief of gastroenterology at Minneapolis VA Health Care System and professor of medicine at the University of Minnesota, Minneapolis, said in a statement.

At the Gastrointestinal Cancers Symposium 2021, she presented data showing that the novel test was able to detect AAs with a sensitivity of 41% and a specificity of 90%.

This sensitivity of the new test is better than or similar to that of currently available stool tests, noted study author C. Jimmy Lin, MD, PhD, MHS, chief scientific officer at Freenome.

The new test had almost double the sensitivity for detecting AAs (41% vs. 24%) as the fecal immunochemical test (FIT), and its sensitivity was comparable to that of FIT-DNA testing (41% vs. 42%).

In addition, it showed much higher sensitivity (41% vs 22%) for detecting AAs than the Epi proColon, a screening blood test that has been approved by the U.S. Food and Drug Administration for detecting methylated septin 9 DNA (mSEPT9).

“What’s special about our company is ... that we use a multinomic technology, meaning we look at DNA, RNA, protein, and other biomarkers – all of these things together,” Dr. Lin told this news organization.

Their platform integrates assays for circulating free DNA, methylation, and proteins using advanced computational biology and machine-learning techniques, which provide a multidimensional view of both tumor- and immune-derived signatures that enable the early detection of cancer.

In contrast to other blood tests that are under development for cancer screening, some of which claim to detect several common cancer types, Freenome is focusing on only colorectal cancer. “There are other companies in the early-detection space, but some of them are doing multicancer screening and have a generalized product,” said Dr. Lin. “Our approach is to focus on a specific cancer type, and we are beginning with colorectal cancer screening, and then will expand to other types.”
 

Better sensitivity

The study that was presented at the meeting evaluated the novel multiomics blood test for AA detection.

Blood samples were obtained from participants in the AI-EMERGE study, a prospective, multicenter study that included primarily average-risk screening patients from 30 clinical sites in the United States and Canada. The study included a total of 542 samples, including 122 histopathologically confirmed AAs and 420 colonoscopy-confirmed negative control samples.

AA sensitivity of the novel test was greater than that with the mSEPT9 test, which is the only blood test currently available for colorectal cancer screening. The new test’s sensitivity was much higher than that of FIT and was comparable to that of FIT-DNA. Sensitivity increased with increasing lesion size and was consistent across location and histology except for serrated lesions, the authors noted in the abstract.

“By combining signatures from both tumor and non–tumor-derived sources, our multiomics signatures detect twice as many AAs as methylation only or single-protein approaches,” Dr. Lin said. “And we have now shown that sensitive AA detection at a level similar to or better than currently available stool tests is achievable in blood, which is necessary for effective early detection and prevention of colorectal cancers.”

The company has begun the regulatory process for having the test approved by the FDA. The company’s goal is to enroll 14,000 participants and have prospectively collected data.

The research was funded by Freenome. Dr. Lin is the chief scientific officer at Freenome and has relationships with Labroots, Natera, and Neon Therapeutics. Dr. Shaukat has relationships with Freenome and Iterative Scopes.

This article was updated 2/2/21.

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

A novel blood test has shown promise for colorectal cancer screening.

The “multiomics” test, under development by Freenome, has previously been shown to detect early-stage (I/II) colorectal cancer with a sensitivity of 94% and a specificity of 94%.

A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (AAs).

“The ability to detect advanced adenomas is incredibly important because we can remove them before they become cancerous,” senior author Aasma Shaukat, MD, MPH, chief of gastroenterology at Minneapolis VA Health Care System and professor of medicine at the University of Minnesota, Minneapolis, said in a statement.

At the Gastrointestinal Cancers Symposium 2021, she presented data showing that the novel test was able to detect AAs with a sensitivity of 41% and a specificity of 90%.

This sensitivity of the new test is better than or similar to that of currently available stool tests, noted study author C. Jimmy Lin, MD, PhD, MHS, chief scientific officer at Freenome.

The new test had almost double the sensitivity for detecting AAs (41% vs. 24%) as the fecal immunochemical test (FIT), and its sensitivity was comparable to that of FIT-DNA testing (41% vs. 42%).

In addition, it showed much higher sensitivity (41% vs 22%) for detecting AAs than the Epi proColon, a screening blood test that has been approved by the U.S. Food and Drug Administration for detecting methylated septin 9 DNA (mSEPT9).

“What’s special about our company is ... that we use a multinomic technology, meaning we look at DNA, RNA, protein, and other biomarkers – all of these things together,” Dr. Lin told this news organization.

Their platform integrates assays for circulating free DNA, methylation, and proteins using advanced computational biology and machine-learning techniques, which provide a multidimensional view of both tumor- and immune-derived signatures that enable the early detection of cancer.

In contrast to other blood tests that are under development for cancer screening, some of which claim to detect several common cancer types, Freenome is focusing on only colorectal cancer. “There are other companies in the early-detection space, but some of them are doing multicancer screening and have a generalized product,” said Dr. Lin. “Our approach is to focus on a specific cancer type, and we are beginning with colorectal cancer screening, and then will expand to other types.”
 

Better sensitivity

The study that was presented at the meeting evaluated the novel multiomics blood test for AA detection.

Blood samples were obtained from participants in the AI-EMERGE study, a prospective, multicenter study that included primarily average-risk screening patients from 30 clinical sites in the United States and Canada. The study included a total of 542 samples, including 122 histopathologically confirmed AAs and 420 colonoscopy-confirmed negative control samples.

AA sensitivity of the novel test was greater than that with the mSEPT9 test, which is the only blood test currently available for colorectal cancer screening. The new test’s sensitivity was much higher than that of FIT and was comparable to that of FIT-DNA. Sensitivity increased with increasing lesion size and was consistent across location and histology except for serrated lesions, the authors noted in the abstract.

“By combining signatures from both tumor and non–tumor-derived sources, our multiomics signatures detect twice as many AAs as methylation only or single-protein approaches,” Dr. Lin said. “And we have now shown that sensitive AA detection at a level similar to or better than currently available stool tests is achievable in blood, which is necessary for effective early detection and prevention of colorectal cancers.”

The company has begun the regulatory process for having the test approved by the FDA. The company’s goal is to enroll 14,000 participants and have prospectively collected data.

The research was funded by Freenome. Dr. Lin is the chief scientific officer at Freenome and has relationships with Labroots, Natera, and Neon Therapeutics. Dr. Shaukat has relationships with Freenome and Iterative Scopes.

This article was updated 2/2/21.

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

In a recent international survey, dermatologists both in the United States and abroad acknowledged major gaps in their competence to provide high-quality care to reproductive-age women with psoriasis, Jenny Murase, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

©monkeybusinessimages/Thinkstock

“In Germany, the UK, and the United States, dermatologists face challenges in discussing pregnancy and child-bearing aspiration with women of reproductive age, in recommending compatible treatments during pregnancy, and engaging patients in the shared decision-making process. These challenges may exist due to suboptimal knowledge, skills, confidence, and attitude in respective areas of care,” said Dr. Murase, a dermatologist at the University of California, San Francisco, and coeditor-in-chief of the International Journal of Women’s Dermatology.

• Forty-seven percent of respondents considered their knowledge of the impact of psoriasis on women’s reproductive health to be suboptimal. This knowledge gap was most common among American dermatologists, 59% of whom rated themselves as having suboptimal knowledge, and least common among German practitioners, only 27% of whom reported deficiencies in this area.

Fifty percent of dermatologists rated themselves as having suboptimal skills in discussing contraceptive methods with their psoriasis patients of childbearing potential.

• Forty-eight percent of respondents – and 59% of the American dermatologists – indicated they prefer to leave pregnancy-related discussions to ob.gyns.
• Fifty-five percent of dermatologists had only limited knowledge of the safety data and indications for prescribing biologic therapies before, during, and after pregnancy. Respondents gave themselves an average score of 58 out of 100 in terms of their confidence in prescribing biologics during pregnancy, compared to 74 out of 100 when prescribing before or after pregnancy.
• Forty-eight percent of participants indicated they had suboptimal skills in helping patients counter obstacles to treatment adherence.

Consideration of treatment of psoriasis in pregnancy requires balancing potential medication risks to the fetus versus the possible maternal and fetal harms of under- or nontreatment of their chronic inflammatory skin disease. It’s a matter that calls for shared decision-making between dermatologist and patient. But the survey showed that shared decision-making was often poorly integrated into clinical practice. Ninety-seven percent of the U.S. dermatologists were unaware of the existence of shared decision-making practice guidelines or models, as were 80% of UK respondents and 85% of the Germans. Of the relatively few dermatologists who were aware of such guidance, nearly half dismissed it as inapplicable to their clinical practice. More than one-third of respondents admitted having suboptimal skills in assessing their patients’ desired level of involvement in medical decisions. And one-third of the German dermatologists and roughly one-quarter of those from the United States and United Kingdom reported feeling pressure to make treatment decisions quickly and without patient input.

Dr. Murase added that the survey findings make a strong case for future interventions designed to help dermatologists appreciate the value of shared decision-making and develop the requisite patient-engagement skills. Dr. Murase reported serving as a paid consultant to UCB Pharma, which funded the survey via an educational grant.

bjancin@mdedge.com

In a recent international survey, dermatologists both in the United States and abroad acknowledged major gaps in their competence to provide high-quality care to reproductive-age women with psoriasis, Jenny Murase, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

©monkeybusinessimages/Thinkstock

“In Germany, the UK, and the United States, dermatologists face challenges in discussing pregnancy and child-bearing aspiration with women of reproductive age, in recommending compatible treatments during pregnancy, and engaging patients in the shared decision-making process. These challenges may exist due to suboptimal knowledge, skills, confidence, and attitude in respective areas of care,” said Dr. Murase, a dermatologist at the University of California, San Francisco, and coeditor-in-chief of the International Journal of Women’s Dermatology.

• Forty-seven percent of respondents considered their knowledge of the impact of psoriasis on women’s reproductive health to be suboptimal. This knowledge gap was most common among American dermatologists, 59% of whom rated themselves as having suboptimal knowledge, and least common among German practitioners, only 27% of whom reported deficiencies in this area.

Fifty percent of dermatologists rated themselves as having suboptimal skills in discussing contraceptive methods with their psoriasis patients of childbearing potential.

• Forty-eight percent of respondents – and 59% of the American dermatologists – indicated they prefer to leave pregnancy-related discussions to ob.gyns.
• Fifty-five percent of dermatologists had only limited knowledge of the safety data and indications for prescribing biologic therapies before, during, and after pregnancy. Respondents gave themselves an average score of 58 out of 100 in terms of their confidence in prescribing biologics during pregnancy, compared to 74 out of 100 when prescribing before or after pregnancy.
• Forty-eight percent of participants indicated they had suboptimal skills in helping patients counter obstacles to treatment adherence.

Consideration of treatment of psoriasis in pregnancy requires balancing potential medication risks to the fetus versus the possible maternal and fetal harms of under- or nontreatment of their chronic inflammatory skin disease. It’s a matter that calls for shared decision-making between dermatologist and patient. But the survey showed that shared decision-making was often poorly integrated into clinical practice. Ninety-seven percent of the U.S. dermatologists were unaware of the existence of shared decision-making practice guidelines or models, as were 80% of UK respondents and 85% of the Germans. Of the relatively few dermatologists who were aware of such guidance, nearly half dismissed it as inapplicable to their clinical practice. More than one-third of respondents admitted having suboptimal skills in assessing their patients’ desired level of involvement in medical decisions. And one-third of the German dermatologists and roughly one-quarter of those from the United States and United Kingdom reported feeling pressure to make treatment decisions quickly and without patient input.

Dr. Murase added that the survey findings make a strong case for future interventions designed to help dermatologists appreciate the value of shared decision-making and develop the requisite patient-engagement skills. Dr. Murase reported serving as a paid consultant to UCB Pharma, which funded the survey via an educational grant.

bjancin@mdedge.com

In a recent international survey, dermatologists both in the United States and abroad acknowledged major gaps in their competence to provide high-quality care to reproductive-age women with psoriasis, Jenny Murase, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

©monkeybusinessimages/Thinkstock

“In Germany, the UK, and the United States, dermatologists face challenges in discussing pregnancy and child-bearing aspiration with women of reproductive age, in recommending compatible treatments during pregnancy, and engaging patients in the shared decision-making process. These challenges may exist due to suboptimal knowledge, skills, confidence, and attitude in respective areas of care,” said Dr. Murase, a dermatologist at the University of California, San Francisco, and coeditor-in-chief of the International Journal of Women’s Dermatology.

• Forty-seven percent of respondents considered their knowledge of the impact of psoriasis on women’s reproductive health to be suboptimal. This knowledge gap was most common among American dermatologists, 59% of whom rated themselves as having suboptimal knowledge, and least common among German practitioners, only 27% of whom reported deficiencies in this area.

Fifty percent of dermatologists rated themselves as having suboptimal skills in discussing contraceptive methods with their psoriasis patients of childbearing potential.

• Forty-eight percent of respondents – and 59% of the American dermatologists – indicated they prefer to leave pregnancy-related discussions to ob.gyns.
• Fifty-five percent of dermatologists had only limited knowledge of the safety data and indications for prescribing biologic therapies before, during, and after pregnancy. Respondents gave themselves an average score of 58 out of 100 in terms of their confidence in prescribing biologics during pregnancy, compared to 74 out of 100 when prescribing before or after pregnancy.
• Forty-eight percent of participants indicated they had suboptimal skills in helping patients counter obstacles to treatment adherence.

Consideration of treatment of psoriasis in pregnancy requires balancing potential medication risks to the fetus versus the possible maternal and fetal harms of under- or nontreatment of their chronic inflammatory skin disease. It’s a matter that calls for shared decision-making between dermatologist and patient. But the survey showed that shared decision-making was often poorly integrated into clinical practice. Ninety-seven percent of the U.S. dermatologists were unaware of the existence of shared decision-making practice guidelines or models, as were 80% of UK respondents and 85% of the Germans. Of the relatively few dermatologists who were aware of such guidance, nearly half dismissed it as inapplicable to their clinical practice. More than one-third of respondents admitted having suboptimal skills in assessing their patients’ desired level of involvement in medical decisions. And one-third of the German dermatologists and roughly one-quarter of those from the United States and United Kingdom reported feeling pressure to make treatment decisions quickly and without patient input.

Dr. Murase added that the survey findings make a strong case for future interventions designed to help dermatologists appreciate the value of shared decision-making and develop the requisite patient-engagement skills. Dr. Murase reported serving as a paid consultant to UCB Pharma, which funded the survey via an educational grant.

bjancin@mdedge.com

Most patients with active chronic prurigo nodularis are not satisfied with their treatment, according to a large European survey.

The eye-opening results of the 406-patient, 12-country European patient survey indicate “high levels of disbelief in currently available treatment options and an overall dissatisfaction with treatment,” Manuel P. Pereira, MD, PhD, said in presenting the findings at the annual congress of the European Academy of Dermatology and Venereology.
 

Only 5.3% of patients pronounced themselves “very satisfied” with their treatment. Another 28% were “rather satisfied.”

“Remarkably, almost 10% of patients were not being treated for prurigo despite having active disease,” said Dr. Pereira, a dermatologist at the Center for Chronic Pruritus at University Hospital Münster (Germany).

When survey participants were asked to identify their most important unmet treatment needs, 79.5% named improvement of itch, 57.2% sought improvement in skin lesions, and 30.5% wanted better sleep.

The most widely used treatments were emollients, prescribed in 84.5% of patients; topical steroids, in 55.7%; antihistamines, 55.2%; and phototherapy, 42.1%. Far fewer patients were on more potent medications: Cyclosporine, systemic corticosteroids, or other immunosuppressants were prescribed for 21.9% of patients; gabapentin and related compounds in 17%; and topical immunomodulators in 8.6%. Twenty-three percent of patients were on antidepressants.

None of the available treatment options, all of which are off label, received high marks from patients. For example, only 1 in 10 patients on antihistamines during the last 6 months rated the drugs as effective. Topical immunomodulators were deemed effective by 1.1% of patients with active prurigo nodularis; gabapentinoids by 3.1%; phototherapy by 9.9%; and antidepressants were rated as effective for the chronic skin disease by only 2.3% of patients. The top-rated therapies were topical steroids, deemed effective by 12.8% of patients; systemic immunosuppressants, favored by 12.2%; and emollients, deemed effective by 10.5% of patients, even though more than 80% of survey participants were using them.

Dr. Pereira said the survey results highlight a pressing need for guidelines aimed at improving clinical care for patients with chronic prurigo nodularis. The first-ever such guidelines on the diagnosis and management of this debilitating disease, developed by Dr. Pereira and other members of the International Forum for the Study of Itch (IFSI), were recently published in the journal Itch. The new guidelines advocate a multimodal treatment approach incorporating a combination of topical and systemic therapies.

At present, there is no approved treatment for prurigo nodularis. Given the unmet need, however, the pace of research has quickened. Innovative potential treatments in the developmental pipeline include Janus kinase inhibitors, topical phosphodiesterase-4 inhibitors, systemic opioid receptor modulators, and neurokinin-1 receptor antagonists.

The patient survey was funded by the EADV and carried out by the EADV’s Pruritus Task Force as part of the European Prurigo Project. Dr. Pereira reported receiving research funding from the EADV and the German Research Foundation. He is a paid speaker for AbbVie, Galderma, Menlo Therapeutics (now VYNE Therapeutics), Novartis, and Trevi.

bjancin@mdedge.com

Most patients with active chronic prurigo nodularis are not satisfied with their treatment, according to a large European survey.

The eye-opening results of the 406-patient, 12-country European patient survey indicate “high levels of disbelief in currently available treatment options and an overall dissatisfaction with treatment,” Manuel P. Pereira, MD, PhD, said in presenting the findings at the annual congress of the European Academy of Dermatology and Venereology.
 

Only 5.3% of patients pronounced themselves “very satisfied” with their treatment. Another 28% were “rather satisfied.”

“Remarkably, almost 10% of patients were not being treated for prurigo despite having active disease,” said Dr. Pereira, a dermatologist at the Center for Chronic Pruritus at University Hospital Münster (Germany).

When survey participants were asked to identify their most important unmet treatment needs, 79.5% named improvement of itch, 57.2% sought improvement in skin lesions, and 30.5% wanted better sleep.

The most widely used treatments were emollients, prescribed in 84.5% of patients; topical steroids, in 55.7%; antihistamines, 55.2%; and phototherapy, 42.1%. Far fewer patients were on more potent medications: Cyclosporine, systemic corticosteroids, or other immunosuppressants were prescribed for 21.9% of patients; gabapentin and related compounds in 17%; and topical immunomodulators in 8.6%. Twenty-three percent of patients were on antidepressants.

None of the available treatment options, all of which are off label, received high marks from patients. For example, only 1 in 10 patients on antihistamines during the last 6 months rated the drugs as effective. Topical immunomodulators were deemed effective by 1.1% of patients with active prurigo nodularis; gabapentinoids by 3.1%; phototherapy by 9.9%; and antidepressants were rated as effective for the chronic skin disease by only 2.3% of patients. The top-rated therapies were topical steroids, deemed effective by 12.8% of patients; systemic immunosuppressants, favored by 12.2%; and emollients, deemed effective by 10.5% of patients, even though more than 80% of survey participants were using them.

Dr. Pereira said the survey results highlight a pressing need for guidelines aimed at improving clinical care for patients with chronic prurigo nodularis. The first-ever such guidelines on the diagnosis and management of this debilitating disease, developed by Dr. Pereira and other members of the International Forum for the Study of Itch (IFSI), were recently published in the journal Itch. The new guidelines advocate a multimodal treatment approach incorporating a combination of topical and systemic therapies.

At present, there is no approved treatment for prurigo nodularis. Given the unmet need, however, the pace of research has quickened. Innovative potential treatments in the developmental pipeline include Janus kinase inhibitors, topical phosphodiesterase-4 inhibitors, systemic opioid receptor modulators, and neurokinin-1 receptor antagonists.

The patient survey was funded by the EADV and carried out by the EADV’s Pruritus Task Force as part of the European Prurigo Project. Dr. Pereira reported receiving research funding from the EADV and the German Research Foundation. He is a paid speaker for AbbVie, Galderma, Menlo Therapeutics (now VYNE Therapeutics), Novartis, and Trevi.

bjancin@mdedge.com

Most patients with active chronic prurigo nodularis are not satisfied with their treatment, according to a large European survey.

The eye-opening results of the 406-patient, 12-country European patient survey indicate “high levels of disbelief in currently available treatment options and an overall dissatisfaction with treatment,” Manuel P. Pereira, MD, PhD, said in presenting the findings at the annual congress of the European Academy of Dermatology and Venereology.
 

Only 5.3% of patients pronounced themselves “very satisfied” with their treatment. Another 28% were “rather satisfied.”

“Remarkably, almost 10% of patients were not being treated for prurigo despite having active disease,” said Dr. Pereira, a dermatologist at the Center for Chronic Pruritus at University Hospital Münster (Germany).

When survey participants were asked to identify their most important unmet treatment needs, 79.5% named improvement of itch, 57.2% sought improvement in skin lesions, and 30.5% wanted better sleep.

The most widely used treatments were emollients, prescribed in 84.5% of patients; topical steroids, in 55.7%; antihistamines, 55.2%; and phototherapy, 42.1%. Far fewer patients were on more potent medications: Cyclosporine, systemic corticosteroids, or other immunosuppressants were prescribed for 21.9% of patients; gabapentin and related compounds in 17%; and topical immunomodulators in 8.6%. Twenty-three percent of patients were on antidepressants.

None of the available treatment options, all of which are off label, received high marks from patients. For example, only 1 in 10 patients on antihistamines during the last 6 months rated the drugs as effective. Topical immunomodulators were deemed effective by 1.1% of patients with active prurigo nodularis; gabapentinoids by 3.1%; phototherapy by 9.9%; and antidepressants were rated as effective for the chronic skin disease by only 2.3% of patients. The top-rated therapies were topical steroids, deemed effective by 12.8% of patients; systemic immunosuppressants, favored by 12.2%; and emollients, deemed effective by 10.5% of patients, even though more than 80% of survey participants were using them.

Dr. Pereira said the survey results highlight a pressing need for guidelines aimed at improving clinical care for patients with chronic prurigo nodularis. The first-ever such guidelines on the diagnosis and management of this debilitating disease, developed by Dr. Pereira and other members of the International Forum for the Study of Itch (IFSI), were recently published in the journal Itch. The new guidelines advocate a multimodal treatment approach incorporating a combination of topical and systemic therapies.

At present, there is no approved treatment for prurigo nodularis. Given the unmet need, however, the pace of research has quickened. Innovative potential treatments in the developmental pipeline include Janus kinase inhibitors, topical phosphodiesterase-4 inhibitors, systemic opioid receptor modulators, and neurokinin-1 receptor antagonists.

The patient survey was funded by the EADV and carried out by the EADV’s Pruritus Task Force as part of the European Prurigo Project. Dr. Pereira reported receiving research funding from the EADV and the German Research Foundation. He is a paid speaker for AbbVie, Galderma, Menlo Therapeutics (now VYNE Therapeutics), Novartis, and Trevi.

bjancin@mdedge.com

The “maskne” phenomenon – that is, new onset or exacerbation of preexisting acne due to prolonged wearing of protective face masks – has become commonplace during the COVID-19 pandemic. Less well appreciated is that rosacea often markedly worsens, too, Giovanni Damiani, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

filadendron/E+

“This is particularly interesting because two inflammatory dermatoses with different pathogenesis are both mechanically and microbiologically triggered by mask use,” observed Dr. Damiani, a dermatologist at the University of Milan.

He presented an observational study of 36 patients with rosacea evaluated before and again 1 month into the strict quarantine imposed in the Milan area during the initial wave of the pandemic. These patients – 23 with papulopustular and 13 with erythematotelangiectatic rosacea – were wearing face masks for at least 6 hours per day during quarantine. Most were using what Dr. Damiani termed “community masks,” meaning they weren’t approved by the European regulatory agency as personal protective equipment.

Every yardstick Dr. Damiani and coinvestigators employed to characterize the patients’ rosacea demonstrated that the dermatosis was significantly worse during the prolonged mask-wearing period. For example, the average prequarantine score on the Global Flushing Severity Scale was 2.56, jumping to 3.97 after a month of masked quarantine. The flushing score climbed from 1.83 to 2.78 in the subgroup with papulopustular rosacea, and from 3.85 to 6.08 in patients with erythematotelangiectatic rosacea. Scores on the Clinician’s Erythema Assessment rose from 1.09 to 1.7 in the papulopustular rosacea patients, and from 2.46 to 3.54 in those with erythematotelangiectatic rosacea.

Scores on the Dermatology Life Quality Index climbed from 7.35 prequarantine to 10.65 in the subgroup with papulopustular rosacea and from 5.15 to 8.69 in patients with erythematotelangiectatic rosacea. Investigator Global Assessment and Patient’s Self-Assessment scores also deteriorated significantly after a month in masked quarantine.

Clinically, the mask-aggravated rosacea, or “maskacea,” was mainly localized to the dorsal lower third of the nose as well as the cheeks. The ocular and perioral areas and the chin were least affected.

Dr. Damiani advised his colleagues to intensify therapy promptly when patients report any worsening of their preexisting rosacea in connection with use of face masks. He has found this condition is often relatively treatment resistant so long as affected patients continue to wear face masks as an essential tool in preventing transmission of COVID-19.

The dermatologist noted that not all face masks are equal offenders when it comes to aggravating common facial dermatoses. During the spring 2020 pandemic quarantine in Milan, 11.6% of 318 mask wearers, none health care professionals, presented to Dr. Damiani and coinvestigators for treatment of facial dermatoses. The facial dermatosis rate was 5.4% among 168 users of masks bearing the European Union CE mark signifying the devices met relevant safety and performance standards, compared with 18.7% in 150 users of community masks with no CE mark. The rate of irritant contact dermatitis was zero with the CE mark masks and 4.7% with the community masks.

During quarantine, however, these patients wore their protective face masks for only a limited time, since for the most part they were restricted to home. In contrast, during the first week after the quarantine was lifted in early May and the daily hours of mask use increased, facial dermatoses were diagnosed in 8.7% of 23 users of CE-approved masks, compared with 45% of 71 wearers of community masks. Dr. Damiani and colleagues diagnosed irritant contact dermatitis in 16% of the community mask wearers post quarantine, but in not a single user of a mask bearing the CE mark.

The National Rosacea Society has issued patient guidance on avoiding rosacea flare-ups during the Covid-19 pandemic.

Dr. Damiani reported having no financial conflicts regarding his study.

bjancin@mdedge.com

The “maskne” phenomenon – that is, new onset or exacerbation of preexisting acne due to prolonged wearing of protective face masks – has become commonplace during the COVID-19 pandemic. Less well appreciated is that rosacea often markedly worsens, too, Giovanni Damiani, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

filadendron/E+

“This is particularly interesting because two inflammatory dermatoses with different pathogenesis are both mechanically and microbiologically triggered by mask use,” observed Dr. Damiani, a dermatologist at the University of Milan.

He presented an observational study of 36 patients with rosacea evaluated before and again 1 month into the strict quarantine imposed in the Milan area during the initial wave of the pandemic. These patients – 23 with papulopustular and 13 with erythematotelangiectatic rosacea – were wearing face masks for at least 6 hours per day during quarantine. Most were using what Dr. Damiani termed “community masks,” meaning they weren’t approved by the European regulatory agency as personal protective equipment.

Every yardstick Dr. Damiani and coinvestigators employed to characterize the patients’ rosacea demonstrated that the dermatosis was significantly worse during the prolonged mask-wearing period. For example, the average prequarantine score on the Global Flushing Severity Scale was 2.56, jumping to 3.97 after a month of masked quarantine. The flushing score climbed from 1.83 to 2.78 in the subgroup with papulopustular rosacea, and from 3.85 to 6.08 in patients with erythematotelangiectatic rosacea. Scores on the Clinician’s Erythema Assessment rose from 1.09 to 1.7 in the papulopustular rosacea patients, and from 2.46 to 3.54 in those with erythematotelangiectatic rosacea.

Scores on the Dermatology Life Quality Index climbed from 7.35 prequarantine to 10.65 in the subgroup with papulopustular rosacea and from 5.15 to 8.69 in patients with erythematotelangiectatic rosacea. Investigator Global Assessment and Patient’s Self-Assessment scores also deteriorated significantly after a month in masked quarantine.

Clinically, the mask-aggravated rosacea, or “maskacea,” was mainly localized to the dorsal lower third of the nose as well as the cheeks. The ocular and perioral areas and the chin were least affected.

Dr. Damiani advised his colleagues to intensify therapy promptly when patients report any worsening of their preexisting rosacea in connection with use of face masks. He has found this condition is often relatively treatment resistant so long as affected patients continue to wear face masks as an essential tool in preventing transmission of COVID-19.

The dermatologist noted that not all face masks are equal offenders when it comes to aggravating common facial dermatoses. During the spring 2020 pandemic quarantine in Milan, 11.6% of 318 mask wearers, none health care professionals, presented to Dr. Damiani and coinvestigators for treatment of facial dermatoses. The facial dermatosis rate was 5.4% among 168 users of masks bearing the European Union CE mark signifying the devices met relevant safety and performance standards, compared with 18.7% in 150 users of community masks with no CE mark. The rate of irritant contact dermatitis was zero with the CE mark masks and 4.7% with the community masks.

During quarantine, however, these patients wore their protective face masks for only a limited time, since for the most part they were restricted to home. In contrast, during the first week after the quarantine was lifted in early May and the daily hours of mask use increased, facial dermatoses were diagnosed in 8.7% of 23 users of CE-approved masks, compared with 45% of 71 wearers of community masks. Dr. Damiani and colleagues diagnosed irritant contact dermatitis in 16% of the community mask wearers post quarantine, but in not a single user of a mask bearing the CE mark.

The National Rosacea Society has issued patient guidance on avoiding rosacea flare-ups during the Covid-19 pandemic.

Dr. Damiani reported having no financial conflicts regarding his study.

bjancin@mdedge.com

The “maskne” phenomenon – that is, new onset or exacerbation of preexisting acne due to prolonged wearing of protective face masks – has become commonplace during the COVID-19 pandemic. Less well appreciated is that rosacea often markedly worsens, too, Giovanni Damiani, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

filadendron/E+

“This is particularly interesting because two inflammatory dermatoses with different pathogenesis are both mechanically and microbiologically triggered by mask use,” observed Dr. Damiani, a dermatologist at the University of Milan.

He presented an observational study of 36 patients with rosacea evaluated before and again 1 month into the strict quarantine imposed in the Milan area during the initial wave of the pandemic. These patients – 23 with papulopustular and 13 with erythematotelangiectatic rosacea – were wearing face masks for at least 6 hours per day during quarantine. Most were using what Dr. Damiani termed “community masks,” meaning they weren’t approved by the European regulatory agency as personal protective equipment.

Every yardstick Dr. Damiani and coinvestigators employed to characterize the patients’ rosacea demonstrated that the dermatosis was significantly worse during the prolonged mask-wearing period. For example, the average prequarantine score on the Global Flushing Severity Scale was 2.56, jumping to 3.97 after a month of masked quarantine. The flushing score climbed from 1.83 to 2.78 in the subgroup with papulopustular rosacea, and from 3.85 to 6.08 in patients with erythematotelangiectatic rosacea. Scores on the Clinician’s Erythema Assessment rose from 1.09 to 1.7 in the papulopustular rosacea patients, and from 2.46 to 3.54 in those with erythematotelangiectatic rosacea.

Scores on the Dermatology Life Quality Index climbed from 7.35 prequarantine to 10.65 in the subgroup with papulopustular rosacea and from 5.15 to 8.69 in patients with erythematotelangiectatic rosacea. Investigator Global Assessment and Patient’s Self-Assessment scores also deteriorated significantly after a month in masked quarantine.

Clinically, the mask-aggravated rosacea, or “maskacea,” was mainly localized to the dorsal lower third of the nose as well as the cheeks. The ocular and perioral areas and the chin were least affected.

Dr. Damiani advised his colleagues to intensify therapy promptly when patients report any worsening of their preexisting rosacea in connection with use of face masks. He has found this condition is often relatively treatment resistant so long as affected patients continue to wear face masks as an essential tool in preventing transmission of COVID-19.

The dermatologist noted that not all face masks are equal offenders when it comes to aggravating common facial dermatoses. During the spring 2020 pandemic quarantine in Milan, 11.6% of 318 mask wearers, none health care professionals, presented to Dr. Damiani and coinvestigators for treatment of facial dermatoses. The facial dermatosis rate was 5.4% among 168 users of masks bearing the European Union CE mark signifying the devices met relevant safety and performance standards, compared with 18.7% in 150 users of community masks with no CE mark. The rate of irritant contact dermatitis was zero with the CE mark masks and 4.7% with the community masks.

During quarantine, however, these patients wore their protective face masks for only a limited time, since for the most part they were restricted to home. In contrast, during the first week after the quarantine was lifted in early May and the daily hours of mask use increased, facial dermatoses were diagnosed in 8.7% of 23 users of CE-approved masks, compared with 45% of 71 wearers of community masks. Dr. Damiani and colleagues diagnosed irritant contact dermatitis in 16% of the community mask wearers post quarantine, but in not a single user of a mask bearing the CE mark.

The National Rosacea Society has issued patient guidance on avoiding rosacea flare-ups during the Covid-19 pandemic.

Dr. Damiani reported having no financial conflicts regarding his study.

bjancin@mdedge.com

Combining standard neoadjuvant chemotherapy for locally advanced esophageal cancer with either radiation or docetaxel did not increase the risk of surgical complications, investigators in the JCOG1109 trial reported.

The trial included patients with clinical stage IB, II, or III (non-T4) thoracic esophageal cancer randomly assigned to cisplatin plus 5-fluorouracil (CF), CF plus radiotherapy (CF-RT), or docetaxel plus CF (DCF) prior to surgery.

Results showed the type of therapy did not significantly affect risk for either perioperative complications or deaths. There was also evidence to suggest that a lower risk of postoperative complications with DCF compared with CF might translate into improved prognosis with the addition of docetaxel, said Kazuo Koyanagi, MD, PhD, of National Cancer Center Hospital in Tokyo.

Dr. Koyanagi presented these results at the 2021 Gastrointestinal Cancers Symposium.

“Based on these results, we could say that preoperative chemotherapy with DCF and CF-RT didn’t increase the risk of postoperative complications when compared with standard CF, and whether the decrease in the risk in the DCF would be reflected in the improvement of prognosis should be examined in the future,” Dr. Koyanagi said.
 

Trial details

The JCOG1109 trial is a three-arm, phase 3 trial designed to see whether adding docetaxel or radiation to CF could improve outcomes. In the analysis presented here, the investigators examined whether the choice of regimen could affect the safety of esophagectomy, and they looked for risk factors for postoperative complications.

Patients with histologically proven squamous cell, adenosquamous, or basaloid carcinoma with locally advanced lesions in the thoracic esophagus were eligible.

The patients had to have good performance status (Eastern Cooperative Oncology Group 0 or 1) and could not have had chemotherapy, radiotherapy, or hormonal therapy for any cancer, or prior therapy for esophageal cancer except for complete endoscopic mucosal or submucosal dissection.

A total of 601 patients were enrolled and randomized to receive one of the following treatments:

• CF, with cisplatin at a dose of 80 mg/m² on day 1 and 5-fluorouracil at 800 mg/m² on days 1-5 every 3 weeks for two cycles (199 assigned; 185 had surgery)
• DCF, with cisplatin at 70 mg/m² on day 1, 5-fluorouracil at 750 mg/m² on days 1-5, and docetaxel at 70 mg/m² on day 1 every 3 weeks for three cycles (202 assigned; 183 had surgery)
• CF-RT, with cisplatin at 75 mg/m² on day 1, 5-fluorouracil at 1,000 mg/m² on days 1-4 every 4 weeks for two cycles, plus 1.8 Gy radiation divided into 23 fractions for a total of 41.4 Gy (200 assigned; 178 had surgery).

Patient age, body mass index, tumor location, clinical stage and node status were comparable among the treatment groups.

Operative characteristics (duration, blood loss, approach, extent of lymph node dissection) were generally similar between the arms as well, except that significantly fewer lymph nodes were harvested with CF-RT compared with either CF or DCF (median of 49, 58, and 59, respectively).
 

Results

Incidence rates of major postoperative complications – pneumonia, leakage, and recurrent laryngeal nerve paralysis – were generally similar among the groups.

The cumulative rate of grade 2 or greater postoperative complications was significantly lower for DCF than for CF (P = .02), but not for DCF compared with CF-RT (P = .11). The rates were 43.7% with DCF, 47.8% with CF-RT, and 56.2% with CF.

The rate of grade 2 or greater chylothorax (leakage of lymphatics into the pleural space) was significantly higher with CF-RT than CF (5.1% vs. 1.1%, P = .03) but not with DCF vs. CF (3.8% vs. 1.1%, P = .10)

In multivariable analysis controlling for demographic, clinical, and operative characteristics, factors associated with lower risk for complications included:

• Middle esophageal tumor location vs. upper esophageal tumors (relative risk [RR], 0.79; P = .03)
• DCF (RR, 0.79; P = .02)
• A thoracoscopic vs. open approach (RR, 0.77; P = .002).

The only factor associated with higher risk was operative time longer than 492 minutes (RR, 1.26; P = .008).

Dr. Koyanagi said the reasons for the lower lymph node yield and more frequent chylothorax with CF-RT are unclear but may be related to tissue fibrosis from radiation exposure.
 

CROSS talk

“As a North American surgeon, I generally look to CROSS induction chemotherapy for the majority of my patients for both adenocarcinoma and squamous cell carcinoma of the esophagus,” said invited discussant Jonathan Yeung, MD, PhD, of the Princess Margaret Cancer Centre in Toronto.

The CROSS regimen consists of carboplatin titrated to an area under the curve of 2 mg/mL per minute and paclitaxel at 50 mg/m² for 5 weeks with concurrent radiotherapy to a total dose of 41.4 Gy delivered in 23 fractions, 5 days per week.

Dr. Yeung noted that, of the eligible patients in JCOG1109, 92% of those assigned to DCF actually underwent surgery, and 90% of those assigned to CF-RT went on to surgery, compared with 98% of patients who had surgery in the CROSS trial, suggesting that the DCF and CF-RT regimens may be more toxic.

He also noted that the lower lymph node harvest seen with CF-RT was seen in other studies.

“I must say I’m always impressed by the lymph node yields that our Japanese colleagues can obtain at surgery, but this lower lymph node yield is also borne out in the CROSS data, where there are less lymph nodes harvested following chemoradiotherapy,” he said.

A higher rate of chylothorax with CF-RT was also seen in patients in the CROSS trial who were randomized to receive radiation compared with those who received chemotherapy alone.

“I await the final results to see if there is ultimately better survival,” Dr. Yeung said.

JCOG1109 was supported by grants from the National Cancer Center Research and Development Funds and Agency for Medical Research and Development of Japan. Dr. Koyanagi and Dr. Yeung reported no conflicts of interest.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Combining standard neoadjuvant chemotherapy for locally advanced esophageal cancer with either radiation or docetaxel did not increase the risk of surgical complications, investigators in the JCOG1109 trial reported.

The trial included patients with clinical stage IB, II, or III (non-T4) thoracic esophageal cancer randomly assigned to cisplatin plus 5-fluorouracil (CF), CF plus radiotherapy (CF-RT), or docetaxel plus CF (DCF) prior to surgery.

Results showed the type of therapy did not significantly affect risk for either perioperative complications or deaths. There was also evidence to suggest that a lower risk of postoperative complications with DCF compared with CF might translate into improved prognosis with the addition of docetaxel, said Kazuo Koyanagi, MD, PhD, of National Cancer Center Hospital in Tokyo.

Dr. Koyanagi presented these results at the 2021 Gastrointestinal Cancers Symposium.

“Based on these results, we could say that preoperative chemotherapy with DCF and CF-RT didn’t increase the risk of postoperative complications when compared with standard CF, and whether the decrease in the risk in the DCF would be reflected in the improvement of prognosis should be examined in the future,” Dr. Koyanagi said.
 

Trial details

The JCOG1109 trial is a three-arm, phase 3 trial designed to see whether adding docetaxel or radiation to CF could improve outcomes. In the analysis presented here, the investigators examined whether the choice of regimen could affect the safety of esophagectomy, and they looked for risk factors for postoperative complications.

Patients with histologically proven squamous cell, adenosquamous, or basaloid carcinoma with locally advanced lesions in the thoracic esophagus were eligible.

The patients had to have good performance status (Eastern Cooperative Oncology Group 0 or 1) and could not have had chemotherapy, radiotherapy, or hormonal therapy for any cancer, or prior therapy for esophageal cancer except for complete endoscopic mucosal or submucosal dissection.

A total of 601 patients were enrolled and randomized to receive one of the following treatments:

• CF, with cisplatin at a dose of 80 mg/m² on day 1 and 5-fluorouracil at 800 mg/m² on days 1-5 every 3 weeks for two cycles (199 assigned; 185 had surgery)
• DCF, with cisplatin at 70 mg/m² on day 1, 5-fluorouracil at 750 mg/m² on days 1-5, and docetaxel at 70 mg/m² on day 1 every 3 weeks for three cycles (202 assigned; 183 had surgery)
• CF-RT, with cisplatin at 75 mg/m² on day 1, 5-fluorouracil at 1,000 mg/m² on days 1-4 every 4 weeks for two cycles, plus 1.8 Gy radiation divided into 23 fractions for a total of 41.4 Gy (200 assigned; 178 had surgery).

Patient age, body mass index, tumor location, clinical stage and node status were comparable among the treatment groups.

Operative characteristics (duration, blood loss, approach, extent of lymph node dissection) were generally similar between the arms as well, except that significantly fewer lymph nodes were harvested with CF-RT compared with either CF or DCF (median of 49, 58, and 59, respectively).
 

Results

Incidence rates of major postoperative complications – pneumonia, leakage, and recurrent laryngeal nerve paralysis – were generally similar among the groups.

The cumulative rate of grade 2 or greater postoperative complications was significantly lower for DCF than for CF (P = .02), but not for DCF compared with CF-RT (P = .11). The rates were 43.7% with DCF, 47.8% with CF-RT, and 56.2% with CF.

The rate of grade 2 or greater chylothorax (leakage of lymphatics into the pleural space) was significantly higher with CF-RT than CF (5.1% vs. 1.1%, P = .03) but not with DCF vs. CF (3.8% vs. 1.1%, P = .10)

In multivariable analysis controlling for demographic, clinical, and operative characteristics, factors associated with lower risk for complications included:

• Middle esophageal tumor location vs. upper esophageal tumors (relative risk [RR], 0.79; P = .03)
• DCF (RR, 0.79; P = .02)
• A thoracoscopic vs. open approach (RR, 0.77; P = .002).

The only factor associated with higher risk was operative time longer than 492 minutes (RR, 1.26; P = .008).

Dr. Koyanagi said the reasons for the lower lymph node yield and more frequent chylothorax with CF-RT are unclear but may be related to tissue fibrosis from radiation exposure.
 

CROSS talk

“As a North American surgeon, I generally look to CROSS induction chemotherapy for the majority of my patients for both adenocarcinoma and squamous cell carcinoma of the esophagus,” said invited discussant Jonathan Yeung, MD, PhD, of the Princess Margaret Cancer Centre in Toronto.

The CROSS regimen consists of carboplatin titrated to an area under the curve of 2 mg/mL per minute and paclitaxel at 50 mg/m² for 5 weeks with concurrent radiotherapy to a total dose of 41.4 Gy delivered in 23 fractions, 5 days per week.

Dr. Yeung noted that, of the eligible patients in JCOG1109, 92% of those assigned to DCF actually underwent surgery, and 90% of those assigned to CF-RT went on to surgery, compared with 98% of patients who had surgery in the CROSS trial, suggesting that the DCF and CF-RT regimens may be more toxic.

He also noted that the lower lymph node harvest seen with CF-RT was seen in other studies.

“I must say I’m always impressed by the lymph node yields that our Japanese colleagues can obtain at surgery, but this lower lymph node yield is also borne out in the CROSS data, where there are less lymph nodes harvested following chemoradiotherapy,” he said.

A higher rate of chylothorax with CF-RT was also seen in patients in the CROSS trial who were randomized to receive radiation compared with those who received chemotherapy alone.

“I await the final results to see if there is ultimately better survival,” Dr. Yeung said.

JCOG1109 was supported by grants from the National Cancer Center Research and Development Funds and Agency for Medical Research and Development of Japan. Dr. Koyanagi and Dr. Yeung reported no conflicts of interest.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Combining standard neoadjuvant chemotherapy for locally advanced esophageal cancer with either radiation or docetaxel did not increase the risk of surgical complications, investigators in the JCOG1109 trial reported.

The trial included patients with clinical stage IB, II, or III (non-T4) thoracic esophageal cancer randomly assigned to cisplatin plus 5-fluorouracil (CF), CF plus radiotherapy (CF-RT), or docetaxel plus CF (DCF) prior to surgery.

Results showed the type of therapy did not significantly affect risk for either perioperative complications or deaths. There was also evidence to suggest that a lower risk of postoperative complications with DCF compared with CF might translate into improved prognosis with the addition of docetaxel, said Kazuo Koyanagi, MD, PhD, of National Cancer Center Hospital in Tokyo.

Dr. Koyanagi presented these results at the 2021 Gastrointestinal Cancers Symposium.

“Based on these results, we could say that preoperative chemotherapy with DCF and CF-RT didn’t increase the risk of postoperative complications when compared with standard CF, and whether the decrease in the risk in the DCF would be reflected in the improvement of prognosis should be examined in the future,” Dr. Koyanagi said.
 

Trial details

The JCOG1109 trial is a three-arm, phase 3 trial designed to see whether adding docetaxel or radiation to CF could improve outcomes. In the analysis presented here, the investigators examined whether the choice of regimen could affect the safety of esophagectomy, and they looked for risk factors for postoperative complications.

Patients with histologically proven squamous cell, adenosquamous, or basaloid carcinoma with locally advanced lesions in the thoracic esophagus were eligible.

The patients had to have good performance status (Eastern Cooperative Oncology Group 0 or 1) and could not have had chemotherapy, radiotherapy, or hormonal therapy for any cancer, or prior therapy for esophageal cancer except for complete endoscopic mucosal or submucosal dissection.

A total of 601 patients were enrolled and randomized to receive one of the following treatments:

• CF, with cisplatin at a dose of 80 mg/m² on day 1 and 5-fluorouracil at 800 mg/m² on days 1-5 every 3 weeks for two cycles (199 assigned; 185 had surgery)
• DCF, with cisplatin at 70 mg/m² on day 1, 5-fluorouracil at 750 mg/m² on days 1-5, and docetaxel at 70 mg/m² on day 1 every 3 weeks for three cycles (202 assigned; 183 had surgery)
• CF-RT, with cisplatin at 75 mg/m² on day 1, 5-fluorouracil at 1,000 mg/m² on days 1-4 every 4 weeks for two cycles, plus 1.8 Gy radiation divided into 23 fractions for a total of 41.4 Gy (200 assigned; 178 had surgery).

Patient age, body mass index, tumor location, clinical stage and node status were comparable among the treatment groups.

Operative characteristics (duration, blood loss, approach, extent of lymph node dissection) were generally similar between the arms as well, except that significantly fewer lymph nodes were harvested with CF-RT compared with either CF or DCF (median of 49, 58, and 59, respectively).
 

Results

Incidence rates of major postoperative complications – pneumonia, leakage, and recurrent laryngeal nerve paralysis – were generally similar among the groups.

The cumulative rate of grade 2 or greater postoperative complications was significantly lower for DCF than for CF (P = .02), but not for DCF compared with CF-RT (P = .11). The rates were 43.7% with DCF, 47.8% with CF-RT, and 56.2% with CF.

The rate of grade 2 or greater chylothorax (leakage of lymphatics into the pleural space) was significantly higher with CF-RT than CF (5.1% vs. 1.1%, P = .03) but not with DCF vs. CF (3.8% vs. 1.1%, P = .10)

In multivariable analysis controlling for demographic, clinical, and operative characteristics, factors associated with lower risk for complications included:

• Middle esophageal tumor location vs. upper esophageal tumors (relative risk [RR], 0.79; P = .03)
• DCF (RR, 0.79; P = .02)
• A thoracoscopic vs. open approach (RR, 0.77; P = .002).

The only factor associated with higher risk was operative time longer than 492 minutes (RR, 1.26; P = .008).

Dr. Koyanagi said the reasons for the lower lymph node yield and more frequent chylothorax with CF-RT are unclear but may be related to tissue fibrosis from radiation exposure.
 

CROSS talk

“As a North American surgeon, I generally look to CROSS induction chemotherapy for the majority of my patients for both adenocarcinoma and squamous cell carcinoma of the esophagus,” said invited discussant Jonathan Yeung, MD, PhD, of the Princess Margaret Cancer Centre in Toronto.

The CROSS regimen consists of carboplatin titrated to an area under the curve of 2 mg/mL per minute and paclitaxel at 50 mg/m² for 5 weeks with concurrent radiotherapy to a total dose of 41.4 Gy delivered in 23 fractions, 5 days per week.

Dr. Yeung noted that, of the eligible patients in JCOG1109, 92% of those assigned to DCF actually underwent surgery, and 90% of those assigned to CF-RT went on to surgery, compared with 98% of patients who had surgery in the CROSS trial, suggesting that the DCF and CF-RT regimens may be more toxic.

He also noted that the lower lymph node harvest seen with CF-RT was seen in other studies.

“I must say I’m always impressed by the lymph node yields that our Japanese colleagues can obtain at surgery, but this lower lymph node yield is also borne out in the CROSS data, where there are less lymph nodes harvested following chemoradiotherapy,” he said.

A higher rate of chylothorax with CF-RT was also seen in patients in the CROSS trial who were randomized to receive radiation compared with those who received chemotherapy alone.

“I await the final results to see if there is ultimately better survival,” Dr. Yeung said.

JCOG1109 was supported by grants from the National Cancer Center Research and Development Funds and Agency for Medical Research and Development of Japan. Dr. Koyanagi and Dr. Yeung reported no conflicts of interest.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) are often treated with chemotherapy, radiotherapy, or both before undergoing surgery, but the optimal regimen in this setting is controversial.

Results from the Alliance A021501 study suggest the reference regimen should be neoadjuvant therapy with modified FOLFIRINOX (oxaliplatin 85 mg/m², irinotecan 180 mg/m², leucovorin 400 mg/m², and infusional 5-fluorouracil 2,400 mg/m² over 46 hours), according to Matthew Katz, MD, FACS, chief of the pancreatic surgery service at the University of Texas MD Anderson Cancer Center, Houston.

This regimen improved survival for patients with PDAC, relative to historical data. For patients who received mFOLFIRINOX, the overall 18-month survival rate was 66.4%. However, when this regimen was combined with hypofractionated radiotherapy, the survival benefit was significantly lower, at 47.3%.

These findings were presented at the 2021 Gastrointestinal Cancers Symposium (GICS), which was held online this year.

“ASCO guidelines recommend that preoperative therapy be administered to patients with localized pancreatic adenocarcinoma who have tumors that have a significant radiographic interface with the major mesenteric blood vessels, as these patients are at high risk for a margin-positive operation and short survival when pancreatectomy is performed de novo,” Dr. Katz explained.

Although both chemotherapy and radiotherapy are used in these patients, there is no consensus as to the best approach, he commented.

The goal of Alliance A021501 “was to define a reference preoperative regimen for future trials of preoperative therapy,” he said.

The cohort included 126 patients who were randomly assigned to receive either mFOLFIRINOX (arm A) or mFOLFIRINOX plus radiotherapy (arm B).

Patients in arm A received eight cycles of neoadjuvant mFOLFIRINOX. Patients in arm B received seven cycles of mFOLFIRINOX followed by 5 days of hypofractionated radiotherapy with either stereotactic body radiotherapy or hypofractionated image-guided radiotherapy.

In either arm, patients who did not experience disease progression underwent pancreatectomy followed by four cycles of adjuvant mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², and infusional 5-fluorouracil 2,400 mg/m² over 46 hours).

The study’s primary endpoint was 18-month overall survival in comparison to a historical control of 50%. “An interim futility analysis was scheduled to be conducted following treatment of 30 patients on each arm,” Dr. Katz said. “Either arm in which 11 or fewer patients underwent [curative] R0 resection on protocol was to be declared futile and closed to further enrollment.

“With 62 evaluable patients in each arm, the final efficacy analysis was powered to detect an improvement in 18-month overall survival of 13% over the historical rate of 50%,” said Dr. Katz. “The two arms would be compared only if both were declared efficacious.”

At the interim analysis, 57% of the first 30 patients in arm A had undergone a resection, vs. 33% in arm B. Therefore, arm B was considered futile and was closed to accrual.

The median overall survival in arm A was 29.8 months. The median event-free survival was 15 months. Nearly half (49%) of patients proceeded to pancreatectomy following neoadjuvant therapy. The R0 resection rate was 88%, the pathologic complete response rate was 0%, and the 18-month overall survival rate was 93.1%.

For the patients in arm B, which had been closed to accrual, the median overall survival was 17.1 months, and the median event-free survival was 10.2 months. About one-third (35%) of patients were able to proceed to pancreatectomy. The R0 resection rate was 74%, the pathologic complete response rate was 11%, and the 18-month overall survival rate was 78.9%.

“Preoperative mFOLFIRINOX was associated with favorable overall survival relative to historical criteria in patients with borderline resectable PDAC, and mFOLFIRINOX with radiation therapy met the predefined futility boundary for R0 resection at interim analysis,” Dr. Katz concluded. “Therefore, mFOLFIRINOX represents a reference perioperative regimen for patients with borderline resectable PDAC.”
 

Further investigation needed

The paper’s discussant, Rebecca A. Snyder, MD, MPH, of the Brody School of Medicine, East Carolina University, Greenville, N.C., emphasized that this study was not designed or powered to directly compare chemotherapy alone with chemotherapy plus radiotherapy in the neoadjuvant setting.

She noted that it is surprising that the radiotherapy arm was closed early. She said the reasons for this remain unclear, although a few possible reasons can be speculated.

“Based on multiple studies in both the adjuvant and neoadjuvant setting, including the Alliance [A021501] trial presented today, there is no convincing randomized data that radiation therapy prolongs survival in any population of unselected patients with pancreatic cancer,” said Dr. Snyder.

“Certainly, follow-up questions still remain, specifically regarding the role for non-SBRT radiation in the preoperative setting, which may be answered by the ongoing PREOPANC-2 and PRODIGE 44 trials,” she said.

She added that the “addition of SBRT in the preoperative setting does not appear to be justified.”

The role of radiotherapy for subsets of patients remains unknown, and future investigation should focus on patient-centered endpoints, such as symptomatic local control rates, Dr. Snyder concluded.

The study was funded by the National Institutes of Health. Dr. Katz has had a consulting or advisory role for AbbVie and Alcresta Therapeutics. Dr. Snyder has disclosed no relevant financial relationships.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

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

Patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) are often treated with chemotherapy, radiotherapy, or both before undergoing surgery, but the optimal regimen in this setting is controversial.

Results from the Alliance A021501 study suggest the reference regimen should be neoadjuvant therapy with modified FOLFIRINOX (oxaliplatin 85 mg/m², irinotecan 180 mg/m², leucovorin 400 mg/m², and infusional 5-fluorouracil 2,400 mg/m² over 46 hours), according to Matthew Katz, MD, FACS, chief of the pancreatic surgery service at the University of Texas MD Anderson Cancer Center, Houston.

This regimen improved survival for patients with PDAC, relative to historical data. For patients who received mFOLFIRINOX, the overall 18-month survival rate was 66.4%. However, when this regimen was combined with hypofractionated radiotherapy, the survival benefit was significantly lower, at 47.3%.

These findings were presented at the 2021 Gastrointestinal Cancers Symposium (GICS), which was held online this year.

“ASCO guidelines recommend that preoperative therapy be administered to patients with localized pancreatic adenocarcinoma who have tumors that have a significant radiographic interface with the major mesenteric blood vessels, as these patients are at high risk for a margin-positive operation and short survival when pancreatectomy is performed de novo,” Dr. Katz explained.

Although both chemotherapy and radiotherapy are used in these patients, there is no consensus as to the best approach, he commented.

The goal of Alliance A021501 “was to define a reference preoperative regimen for future trials of preoperative therapy,” he said.

The cohort included 126 patients who were randomly assigned to receive either mFOLFIRINOX (arm A) or mFOLFIRINOX plus radiotherapy (arm B).

Patients in arm A received eight cycles of neoadjuvant mFOLFIRINOX. Patients in arm B received seven cycles of mFOLFIRINOX followed by 5 days of hypofractionated radiotherapy with either stereotactic body radiotherapy or hypofractionated image-guided radiotherapy.

In either arm, patients who did not experience disease progression underwent pancreatectomy followed by four cycles of adjuvant mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², and infusional 5-fluorouracil 2,400 mg/m² over 46 hours).

The study’s primary endpoint was 18-month overall survival in comparison to a historical control of 50%. “An interim futility analysis was scheduled to be conducted following treatment of 30 patients on each arm,” Dr. Katz said. “Either arm in which 11 or fewer patients underwent [curative] R0 resection on protocol was to be declared futile and closed to further enrollment.

“With 62 evaluable patients in each arm, the final efficacy analysis was powered to detect an improvement in 18-month overall survival of 13% over the historical rate of 50%,” said Dr. Katz. “The two arms would be compared only if both were declared efficacious.”

At the interim analysis, 57% of the first 30 patients in arm A had undergone a resection, vs. 33% in arm B. Therefore, arm B was considered futile and was closed to accrual.

The median overall survival in arm A was 29.8 months. The median event-free survival was 15 months. Nearly half (49%) of patients proceeded to pancreatectomy following neoadjuvant therapy. The R0 resection rate was 88%, the pathologic complete response rate was 0%, and the 18-month overall survival rate was 93.1%.

For the patients in arm B, which had been closed to accrual, the median overall survival was 17.1 months, and the median event-free survival was 10.2 months. About one-third (35%) of patients were able to proceed to pancreatectomy. The R0 resection rate was 74%, the pathologic complete response rate was 11%, and the 18-month overall survival rate was 78.9%.

“Preoperative mFOLFIRINOX was associated with favorable overall survival relative to historical criteria in patients with borderline resectable PDAC, and mFOLFIRINOX with radiation therapy met the predefined futility boundary for R0 resection at interim analysis,” Dr. Katz concluded. “Therefore, mFOLFIRINOX represents a reference perioperative regimen for patients with borderline resectable PDAC.”
 

Further investigation needed

The paper’s discussant, Rebecca A. Snyder, MD, MPH, of the Brody School of Medicine, East Carolina University, Greenville, N.C., emphasized that this study was not designed or powered to directly compare chemotherapy alone with chemotherapy plus radiotherapy in the neoadjuvant setting.

She noted that it is surprising that the radiotherapy arm was closed early. She said the reasons for this remain unclear, although a few possible reasons can be speculated.

“Based on multiple studies in both the adjuvant and neoadjuvant setting, including the Alliance [A021501] trial presented today, there is no convincing randomized data that radiation therapy prolongs survival in any population of unselected patients with pancreatic cancer,” said Dr. Snyder.

“Certainly, follow-up questions still remain, specifically regarding the role for non-SBRT radiation in the preoperative setting, which may be answered by the ongoing PREOPANC-2 and PRODIGE 44 trials,” she said.

She added that the “addition of SBRT in the preoperative setting does not appear to be justified.”

The role of radiotherapy for subsets of patients remains unknown, and future investigation should focus on patient-centered endpoints, such as symptomatic local control rates, Dr. Snyder concluded.

The study was funded by the National Institutes of Health. Dr. Katz has had a consulting or advisory role for AbbVie and Alcresta Therapeutics. Dr. Snyder has disclosed no relevant financial relationships.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

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

Patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) are often treated with chemotherapy, radiotherapy, or both before undergoing surgery, but the optimal regimen in this setting is controversial.

Results from the Alliance A021501 study suggest the reference regimen should be neoadjuvant therapy with modified FOLFIRINOX (oxaliplatin 85 mg/m², irinotecan 180 mg/m², leucovorin 400 mg/m², and infusional 5-fluorouracil 2,400 mg/m² over 46 hours), according to Matthew Katz, MD, FACS, chief of the pancreatic surgery service at the University of Texas MD Anderson Cancer Center, Houston.

This regimen improved survival for patients with PDAC, relative to historical data. For patients who received mFOLFIRINOX, the overall 18-month survival rate was 66.4%. However, when this regimen was combined with hypofractionated radiotherapy, the survival benefit was significantly lower, at 47.3%.

These findings were presented at the 2021 Gastrointestinal Cancers Symposium (GICS), which was held online this year.

“ASCO guidelines recommend that preoperative therapy be administered to patients with localized pancreatic adenocarcinoma who have tumors that have a significant radiographic interface with the major mesenteric blood vessels, as these patients are at high risk for a margin-positive operation and short survival when pancreatectomy is performed de novo,” Dr. Katz explained.

Although both chemotherapy and radiotherapy are used in these patients, there is no consensus as to the best approach, he commented.

The goal of Alliance A021501 “was to define a reference preoperative regimen for future trials of preoperative therapy,” he said.

The cohort included 126 patients who were randomly assigned to receive either mFOLFIRINOX (arm A) or mFOLFIRINOX plus radiotherapy (arm B).

Patients in arm A received eight cycles of neoadjuvant mFOLFIRINOX. Patients in arm B received seven cycles of mFOLFIRINOX followed by 5 days of hypofractionated radiotherapy with either stereotactic body radiotherapy or hypofractionated image-guided radiotherapy.

In either arm, patients who did not experience disease progression underwent pancreatectomy followed by four cycles of adjuvant mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², and infusional 5-fluorouracil 2,400 mg/m² over 46 hours).

The study’s primary endpoint was 18-month overall survival in comparison to a historical control of 50%. “An interim futility analysis was scheduled to be conducted following treatment of 30 patients on each arm,” Dr. Katz said. “Either arm in which 11 or fewer patients underwent [curative] R0 resection on protocol was to be declared futile and closed to further enrollment.

“With 62 evaluable patients in each arm, the final efficacy analysis was powered to detect an improvement in 18-month overall survival of 13% over the historical rate of 50%,” said Dr. Katz. “The two arms would be compared only if both were declared efficacious.”

At the interim analysis, 57% of the first 30 patients in arm A had undergone a resection, vs. 33% in arm B. Therefore, arm B was considered futile and was closed to accrual.

The median overall survival in arm A was 29.8 months. The median event-free survival was 15 months. Nearly half (49%) of patients proceeded to pancreatectomy following neoadjuvant therapy. The R0 resection rate was 88%, the pathologic complete response rate was 0%, and the 18-month overall survival rate was 93.1%.

For the patients in arm B, which had been closed to accrual, the median overall survival was 17.1 months, and the median event-free survival was 10.2 months. About one-third (35%) of patients were able to proceed to pancreatectomy. The R0 resection rate was 74%, the pathologic complete response rate was 11%, and the 18-month overall survival rate was 78.9%.

“Preoperative mFOLFIRINOX was associated with favorable overall survival relative to historical criteria in patients with borderline resectable PDAC, and mFOLFIRINOX with radiation therapy met the predefined futility boundary for R0 resection at interim analysis,” Dr. Katz concluded. “Therefore, mFOLFIRINOX represents a reference perioperative regimen for patients with borderline resectable PDAC.”
 

Further investigation needed

The paper’s discussant, Rebecca A. Snyder, MD, MPH, of the Brody School of Medicine, East Carolina University, Greenville, N.C., emphasized that this study was not designed or powered to directly compare chemotherapy alone with chemotherapy plus radiotherapy in the neoadjuvant setting.

She noted that it is surprising that the radiotherapy arm was closed early. She said the reasons for this remain unclear, although a few possible reasons can be speculated.

“Based on multiple studies in both the adjuvant and neoadjuvant setting, including the Alliance [A021501] trial presented today, there is no convincing randomized data that radiation therapy prolongs survival in any population of unselected patients with pancreatic cancer,” said Dr. Snyder.

“Certainly, follow-up questions still remain, specifically regarding the role for non-SBRT radiation in the preoperative setting, which may be answered by the ongoing PREOPANC-2 and PRODIGE 44 trials,” she said.

She added that the “addition of SBRT in the preoperative setting does not appear to be justified.”

The role of radiotherapy for subsets of patients remains unknown, and future investigation should focus on patient-centered endpoints, such as symptomatic local control rates, Dr. Snyder concluded.

The study was funded by the National Institutes of Health. Dr. Katz has had a consulting or advisory role for AbbVie and Alcresta Therapeutics. Dr. Snyder has disclosed no relevant financial relationships.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

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

For patients with intermediate- or high-risk ductal carcinoma in situ (DCIS) treated with conservative surgery and whole breast irradiation (WBI), adding a boost dose to the tumor bed significantly reduced the risk of recurrence, regardless of WBI fractionation, in the BIG-3-07/TROG 07.01 trial.

Giving a tumor bed boost (TBB) reduced the risk of local recurrence and overall disease recurrence, but there were no significant differences in recurrence rates between conventional WBI and hypofractionated WBI.

Boon Hui Chua, MD, of the University of New South Wales, Sydney, presented these results at the 2020 San Antonio Breast Cancer Symposium.

Dr. Chua and colleagues studied 1,608 women with DCIS resected by conservative surgery. Patients were either younger than 50 years or age 50 and older with at least one of the following risk factors: symptomatic presentation, palpable tumor, multifocal disease, tumor size 1.5 cm or larger, intermediate or high nuclear grade, central necrosis, comedo histology, and/or surgical margins less than 10 mm.

The patients were randomized to treatment in three categories. In randomization A (n = 503), patients were randomized to one of the following treatments:

• WBI at 50 Gy in 25 fractions
• WBI at 42.5 Gy in 16 fractions
• WBI at 50 Gy in 25 fractions plus TBB at 16 Gy in 8 fractions
• WBI at 42.5 Gy in 16 fractions plus TBB at 16 Gy in 8 fractions.

In randomization B (n = 581), patients received WBI at 50 Gy in 25 fractions, with or without TBB at 16 Gy in 8 fractions. In randomization C (n = 524), patients received WBI at 42.5 Gy in 16 fractions, with or without TBB at 16 Gy in 8 fractions.

All patients underwent CT-based radiation planning. WBI was delivered with tangential MV photon beams, and TBB was performed with CT contouring of protocol-defined tumor bed target volumes, with electron or photon energy. The median follow-up was 6.6 years.
 

Giving a boost to better outcomes

The 5-year rate of freedom from local recurrence was 97% for patients who received TBB and 93% for patients who did not (hazard ratio, 0.47; P < .001). The benefit of TBB was consistent across subgroups.

There were no significant differences in 5-year rates of freedom from local recurrence by WBI fractionation, either in randomization A (P = .837) or among all randomized patients (P = .887).

The tests for interactions between TBB and WBI fractionation on local recurrence were not significant in randomization A (P = .89) or in all randomized patients (P = .89).

The risk of overall disease recurrence was lower among patients who had received TBB, with an HR of 0.63 (P = .004). The 5-year rate of freedom from disease recurrence was 97% with TBB and 91% with no boost (P = .002).

There were no significant differences in freedom from disease recurrence rates by WBI fractionation either in randomization A (P = .443) or among all randomized patients (P = .605).

Acute radiation dermatitis occurred in significantly more patients who received TBB (P = .006), as did late breast pain (P = .003), induration or fibrosis (P < .0001), and telangiectasia (P = .02). There were no significant differences by boost status for acute or late fatigue, pneumonitis, cardiac complications, or second malignancies.
 

Reduce the boost dose?

A radiation oncologist who was not involved in this study said that, while the results confirm a benefit of boost dose for patients with non–low-risk DCIS, the doses used in the BIG-3-07 study may be higher than needed to achieve a protective effect.

“Here in America, we usually give 10 Gy in five fractions, and, in many countries, actually, it’s 10 Gy in five fractions, although a few European centers give 16 Gy in eight fractions,” said Alphose Taghian, MD, of Massachusetts General Hospital in Boston.

“I personally only give 10 Gy in five fractions. I am not under the impression that 16 Gy in eight fractions will give better results. The local failure rate is so low, it’s likely that 10 Gy will do the job,” Dr. Taghian said in an interview.

Dr. Taghian noted that raising the dose to 16 Gy increases the risk of fibrosis, as seen in the BIG-3-07 trial.

Nonetheless, the trial demonstrates the benefit of radiation boost dose in patients with high-risk DCIS, he said, adding that the local recurrence-free benefit curves may separate further with longer follow-up.

The study was sponsored by the Trans Tasman Radiation Oncology Group. Dr. Chua and Dr. Taghian reported no conflicts of interest.

For patients with intermediate- or high-risk ductal carcinoma in situ (DCIS) treated with conservative surgery and whole breast irradiation (WBI), adding a boost dose to the tumor bed significantly reduced the risk of recurrence, regardless of WBI fractionation, in the BIG-3-07/TROG 07.01 trial.

Giving a tumor bed boost (TBB) reduced the risk of local recurrence and overall disease recurrence, but there were no significant differences in recurrence rates between conventional WBI and hypofractionated WBI.

Boon Hui Chua, MD, of the University of New South Wales, Sydney, presented these results at the 2020 San Antonio Breast Cancer Symposium.

Dr. Chua and colleagues studied 1,608 women with DCIS resected by conservative surgery. Patients were either younger than 50 years or age 50 and older with at least one of the following risk factors: symptomatic presentation, palpable tumor, multifocal disease, tumor size 1.5 cm or larger, intermediate or high nuclear grade, central necrosis, comedo histology, and/or surgical margins less than 10 mm.

The patients were randomized to treatment in three categories. In randomization A (n = 503), patients were randomized to one of the following treatments:

• WBI at 50 Gy in 25 fractions
• WBI at 42.5 Gy in 16 fractions
• WBI at 50 Gy in 25 fractions plus TBB at 16 Gy in 8 fractions
• WBI at 42.5 Gy in 16 fractions plus TBB at 16 Gy in 8 fractions.

In randomization B (n = 581), patients received WBI at 50 Gy in 25 fractions, with or without TBB at 16 Gy in 8 fractions. In randomization C (n = 524), patients received WBI at 42.5 Gy in 16 fractions, with or without TBB at 16 Gy in 8 fractions.

All patients underwent CT-based radiation planning. WBI was delivered with tangential MV photon beams, and TBB was performed with CT contouring of protocol-defined tumor bed target volumes, with electron or photon energy. The median follow-up was 6.6 years.
 

Giving a boost to better outcomes

The 5-year rate of freedom from local recurrence was 97% for patients who received TBB and 93% for patients who did not (hazard ratio, 0.47; P < .001). The benefit of TBB was consistent across subgroups.

There were no significant differences in 5-year rates of freedom from local recurrence by WBI fractionation, either in randomization A (P = .837) or among all randomized patients (P = .887).

The tests for interactions between TBB and WBI fractionation on local recurrence were not significant in randomization A (P = .89) or in all randomized patients (P = .89).

The risk of overall disease recurrence was lower among patients who had received TBB, with an HR of 0.63 (P = .004). The 5-year rate of freedom from disease recurrence was 97% with TBB and 91% with no boost (P = .002).

There were no significant differences in freedom from disease recurrence rates by WBI fractionation either in randomization A (P = .443) or among all randomized patients (P = .605).

Acute radiation dermatitis occurred in significantly more patients who received TBB (P = .006), as did late breast pain (P = .003), induration or fibrosis (P < .0001), and telangiectasia (P = .02). There were no significant differences by boost status for acute or late fatigue, pneumonitis, cardiac complications, or second malignancies.
 

Reduce the boost dose?

A radiation oncologist who was not involved in this study said that, while the results confirm a benefit of boost dose for patients with non–low-risk DCIS, the doses used in the BIG-3-07 study may be higher than needed to achieve a protective effect.

“Here in America, we usually give 10 Gy in five fractions, and, in many countries, actually, it’s 10 Gy in five fractions, although a few European centers give 16 Gy in eight fractions,” said Alphose Taghian, MD, of Massachusetts General Hospital in Boston.

“I personally only give 10 Gy in five fractions. I am not under the impression that 16 Gy in eight fractions will give better results. The local failure rate is so low, it’s likely that 10 Gy will do the job,” Dr. Taghian said in an interview.

Dr. Taghian noted that raising the dose to 16 Gy increases the risk of fibrosis, as seen in the BIG-3-07 trial.

Nonetheless, the trial demonstrates the benefit of radiation boost dose in patients with high-risk DCIS, he said, adding that the local recurrence-free benefit curves may separate further with longer follow-up.

The study was sponsored by the Trans Tasman Radiation Oncology Group. Dr. Chua and Dr. Taghian reported no conflicts of interest.

For patients with intermediate- or high-risk ductal carcinoma in situ (DCIS) treated with conservative surgery and whole breast irradiation (WBI), adding a boost dose to the tumor bed significantly reduced the risk of recurrence, regardless of WBI fractionation, in the BIG-3-07/TROG 07.01 trial.

Giving a tumor bed boost (TBB) reduced the risk of local recurrence and overall disease recurrence, but there were no significant differences in recurrence rates between conventional WBI and hypofractionated WBI.

Boon Hui Chua, MD, of the University of New South Wales, Sydney, presented these results at the 2020 San Antonio Breast Cancer Symposium.

Dr. Chua and colleagues studied 1,608 women with DCIS resected by conservative surgery. Patients were either younger than 50 years or age 50 and older with at least one of the following risk factors: symptomatic presentation, palpable tumor, multifocal disease, tumor size 1.5 cm or larger, intermediate or high nuclear grade, central necrosis, comedo histology, and/or surgical margins less than 10 mm.

The patients were randomized to treatment in three categories. In randomization A (n = 503), patients were randomized to one of the following treatments:

• WBI at 50 Gy in 25 fractions
• WBI at 42.5 Gy in 16 fractions
• WBI at 50 Gy in 25 fractions plus TBB at 16 Gy in 8 fractions
• WBI at 42.5 Gy in 16 fractions plus TBB at 16 Gy in 8 fractions.

In randomization B (n = 581), patients received WBI at 50 Gy in 25 fractions, with or without TBB at 16 Gy in 8 fractions. In randomization C (n = 524), patients received WBI at 42.5 Gy in 16 fractions, with or without TBB at 16 Gy in 8 fractions.

All patients underwent CT-based radiation planning. WBI was delivered with tangential MV photon beams, and TBB was performed with CT contouring of protocol-defined tumor bed target volumes, with electron or photon energy. The median follow-up was 6.6 years.
 

Giving a boost to better outcomes

The 5-year rate of freedom from local recurrence was 97% for patients who received TBB and 93% for patients who did not (hazard ratio, 0.47; P < .001). The benefit of TBB was consistent across subgroups.

There were no significant differences in 5-year rates of freedom from local recurrence by WBI fractionation, either in randomization A (P = .837) or among all randomized patients (P = .887).

The tests for interactions between TBB and WBI fractionation on local recurrence were not significant in randomization A (P = .89) or in all randomized patients (P = .89).

The risk of overall disease recurrence was lower among patients who had received TBB, with an HR of 0.63 (P = .004). The 5-year rate of freedom from disease recurrence was 97% with TBB and 91% with no boost (P = .002).

There were no significant differences in freedom from disease recurrence rates by WBI fractionation either in randomization A (P = .443) or among all randomized patients (P = .605).

Acute radiation dermatitis occurred in significantly more patients who received TBB (P = .006), as did late breast pain (P = .003), induration or fibrosis (P < .0001), and telangiectasia (P = .02). There were no significant differences by boost status for acute or late fatigue, pneumonitis, cardiac complications, or second malignancies.
 

Reduce the boost dose?

A radiation oncologist who was not involved in this study said that, while the results confirm a benefit of boost dose for patients with non–low-risk DCIS, the doses used in the BIG-3-07 study may be higher than needed to achieve a protective effect.

“Here in America, we usually give 10 Gy in five fractions, and, in many countries, actually, it’s 10 Gy in five fractions, although a few European centers give 16 Gy in eight fractions,” said Alphose Taghian, MD, of Massachusetts General Hospital in Boston.

“I personally only give 10 Gy in five fractions. I am not under the impression that 16 Gy in eight fractions will give better results. The local failure rate is so low, it’s likely that 10 Gy will do the job,” Dr. Taghian said in an interview.

Dr. Taghian noted that raising the dose to 16 Gy increases the risk of fibrosis, as seen in the BIG-3-07 trial.

Nonetheless, the trial demonstrates the benefit of radiation boost dose in patients with high-risk DCIS, he said, adding that the local recurrence-free benefit curves may separate further with longer follow-up.

The study was sponsored by the Trans Tasman Radiation Oncology Group. Dr. Chua and Dr. Taghian reported no conflicts of interest.

A new recommendation for the treatment of patients with gastric cancer has been proposed on the basis of final results from the phase 3 trial GC-07, which showed survival benefit. The trial was conducted by the Japan Clinical Cancer Research Organization.

Adjuvant treatment with S-1 plus docetaxel is now recommended for patients with pathologic stage III gastric cancer who have undergone D2 gastrectomy and who have not received neoadjuvant chemotherapy, say the researchers.

The 3-year relapse-free survival (RFS) and 3-year overall survival rates were significantly superior among patients treated with S-1/docetaxel, compared with those treated with S-1 alone, commented lead study author Kazuhiro Yoshida, PhD, MD, director of Gifu University Hospital and professor and chairman of the department of surgical oncology, Gifu (Japan) University.

“The study met its primary endpoint and improved the RFS [recurrence-free survival],” he said. “Postoperative S-1 plus docetaxel was safe and manageable.”

Dr. Yoshida presented the updated findings of the GC-07 trial at the Gastrointestinal Cancers Symposium (GICS) 2021, which was held online this year.
 

S-1 widely used in Asia

S-1 is a novel oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine. The drug, which is a biochemical modulation of 5-fluorouracil, comprises tegafur and two types of enzyme inhibitor. It is widely used to treat various solid tumors in Asia.

“S1 is a standard postoperative adjuvant chemotherapy for patients with p-stage II/III gastric cancer in Asia,” said Dr. Yoshida, but the “outcome in p-stage III is unsatisfactory,” he added.

The GC-07 trial set out to further investigate the use of this drug in this patient population. Dr. Yoshida and colleagues included 915 patients with stage III gastric cancer who had undergone R0 resection and D2 lymphadenectomy and who tested negative on peritoneal-washing cytology. The patients were randomly assigned to receive either S-1 plus docetaxel or S-1 alone for up to 1 year in the postoperative setting.

The data presented at the meeting are the final results from GC-07. They confirm earlier data.

Previously, a second interim analysis showed that the trial had met its primary endpoint. As a result of that analysis, the study was terminated.

That interim analysis showed that the 3-year RFS of the S-1/docetaxel arm was significantly superior to that of the S-1 arm (65.9% vs. 49.6%; hazard ratio, 0.632; P = .0007).

Now, the final results, at a median follow-up of 48.2 months, show that there were 400 recurrences and 324 deaths. The 3-year RFS was 67.7% in the S-1/docetaxel group, which was significantly superior to the 57.4% reported in the S-1 group (HR, 0.715; P = .0008). Similarly, 3-year overall survival was 77.7% in the S-1/docetaxel group, vs. 71.2% in the S-1 group (HR, 0.742; P = .0076).

At 12 months, 62.7% of patients in the S-1 group had experienced treatment failure, compared with 56.2% in the combination-therapy group.

In addition to reducing overall relapse, treatment with combination therapy also decreased the incidence of relapse at specific sites, compared with S-1 alone. These included reductions in lymphatic recurrence (6.4% vs. 15.0%), hematogenous recurrence (9.7% vs. 15.5%), local recurrence (2.9% vs. 4.4%), and peritoneal recurrence (18.8% vs. 21.4%).

No new safety signals were observed, Dr. Yoshida commented. Grade 3/4 adverse events that occurred more frequently with S-1/docetaxel than with S-1 alone included neutropenia (39.2% vs. 16.4%), leukopenia (22.4% vs. 2.7%), and febrile neutropenia (5.7% vs. 0.4%).

However, the authors noted that, in a subgroup analysis, patients with stage IIIB disease did not derive the same benefit in RFS and overall survival with combination therapy as the patients with stage IIIA or IIIC disease.

The discussant for this paper, Rutika Mehta, MD, MPH, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., highlighted differences in benefit among the subgroups, as well as the finding that patients with stage IIIB appeared to benefit less.

However, she noted that the seventh edition of the American Joint Committee on Cancer TNM classification, which distinguishes patients on the basis of prognostic subgroups, is inaccurate for stage III disease, and this might have affected the study results. Dr. Mehta pointed to a previous analysis in which more than 33% of individuals with stage IIIB disease, determined in accordance with the seventh edition of the AJCC staging system, were reclassified as having stage IIIC disease, as determined using the more recent eighth edition.

“There were also few T2, N0, and N1 patients, making meaningful deductions in these subgroups not possible,” she said.

She said that despite these limitations, these “results are meaningful and impactful, and the combination of docetaxel and S-1 showed better RFS and overall survival than S-1 alone.

“These results do favor a new recommendation for the use of docetaxel plus S-1 for stage III gastric cancer patients after D2 lymphadenectomy,” she concluded.

The study was funded by the Japan Clinical Cancer Research Organization. Dr. Yoshida has received honoraria and research funding from many pharmaceutical companies, as listed in the abstract.

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

A new recommendation for the treatment of patients with gastric cancer has been proposed on the basis of final results from the phase 3 trial GC-07, which showed survival benefit. The trial was conducted by the Japan Clinical Cancer Research Organization.

Adjuvant treatment with S-1 plus docetaxel is now recommended for patients with pathologic stage III gastric cancer who have undergone D2 gastrectomy and who have not received neoadjuvant chemotherapy, say the researchers.

The 3-year relapse-free survival (RFS) and 3-year overall survival rates were significantly superior among patients treated with S-1/docetaxel, compared with those treated with S-1 alone, commented lead study author Kazuhiro Yoshida, PhD, MD, director of Gifu University Hospital and professor and chairman of the department of surgical oncology, Gifu (Japan) University.

“The study met its primary endpoint and improved the RFS [recurrence-free survival],” he said. “Postoperative S-1 plus docetaxel was safe and manageable.”

Dr. Yoshida presented the updated findings of the GC-07 trial at the Gastrointestinal Cancers Symposium (GICS) 2021, which was held online this year.
 

S-1 widely used in Asia

S-1 is a novel oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine. The drug, which is a biochemical modulation of 5-fluorouracil, comprises tegafur and two types of enzyme inhibitor. It is widely used to treat various solid tumors in Asia.

“S1 is a standard postoperative adjuvant chemotherapy for patients with p-stage II/III gastric cancer in Asia,” said Dr. Yoshida, but the “outcome in p-stage III is unsatisfactory,” he added.

The GC-07 trial set out to further investigate the use of this drug in this patient population. Dr. Yoshida and colleagues included 915 patients with stage III gastric cancer who had undergone R0 resection and D2 lymphadenectomy and who tested negative on peritoneal-washing cytology. The patients were randomly assigned to receive either S-1 plus docetaxel or S-1 alone for up to 1 year in the postoperative setting.

The data presented at the meeting are the final results from GC-07. They confirm earlier data.

Previously, a second interim analysis showed that the trial had met its primary endpoint. As a result of that analysis, the study was terminated.

That interim analysis showed that the 3-year RFS of the S-1/docetaxel arm was significantly superior to that of the S-1 arm (65.9% vs. 49.6%; hazard ratio, 0.632; P = .0007).

Now, the final results, at a median follow-up of 48.2 months, show that there were 400 recurrences and 324 deaths. The 3-year RFS was 67.7% in the S-1/docetaxel group, which was significantly superior to the 57.4% reported in the S-1 group (HR, 0.715; P = .0008). Similarly, 3-year overall survival was 77.7% in the S-1/docetaxel group, vs. 71.2% in the S-1 group (HR, 0.742; P = .0076).

At 12 months, 62.7% of patients in the S-1 group had experienced treatment failure, compared with 56.2% in the combination-therapy group.

In addition to reducing overall relapse, treatment with combination therapy also decreased the incidence of relapse at specific sites, compared with S-1 alone. These included reductions in lymphatic recurrence (6.4% vs. 15.0%), hematogenous recurrence (9.7% vs. 15.5%), local recurrence (2.9% vs. 4.4%), and peritoneal recurrence (18.8% vs. 21.4%).

No new safety signals were observed, Dr. Yoshida commented. Grade 3/4 adverse events that occurred more frequently with S-1/docetaxel than with S-1 alone included neutropenia (39.2% vs. 16.4%), leukopenia (22.4% vs. 2.7%), and febrile neutropenia (5.7% vs. 0.4%).

However, the authors noted that, in a subgroup analysis, patients with stage IIIB disease did not derive the same benefit in RFS and overall survival with combination therapy as the patients with stage IIIA or IIIC disease.

The discussant for this paper, Rutika Mehta, MD, MPH, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., highlighted differences in benefit among the subgroups, as well as the finding that patients with stage IIIB appeared to benefit less.

However, she noted that the seventh edition of the American Joint Committee on Cancer TNM classification, which distinguishes patients on the basis of prognostic subgroups, is inaccurate for stage III disease, and this might have affected the study results. Dr. Mehta pointed to a previous analysis in which more than 33% of individuals with stage IIIB disease, determined in accordance with the seventh edition of the AJCC staging system, were reclassified as having stage IIIC disease, as determined using the more recent eighth edition.

“There were also few T2, N0, and N1 patients, making meaningful deductions in these subgroups not possible,” she said.

She said that despite these limitations, these “results are meaningful and impactful, and the combination of docetaxel and S-1 showed better RFS and overall survival than S-1 alone.

“These results do favor a new recommendation for the use of docetaxel plus S-1 for stage III gastric cancer patients after D2 lymphadenectomy,” she concluded.

The study was funded by the Japan Clinical Cancer Research Organization. Dr. Yoshida has received honoraria and research funding from many pharmaceutical companies, as listed in the abstract.

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

A new recommendation for the treatment of patients with gastric cancer has been proposed on the basis of final results from the phase 3 trial GC-07, which showed survival benefit. The trial was conducted by the Japan Clinical Cancer Research Organization.

Adjuvant treatment with S-1 plus docetaxel is now recommended for patients with pathologic stage III gastric cancer who have undergone D2 gastrectomy and who have not received neoadjuvant chemotherapy, say the researchers.

The 3-year relapse-free survival (RFS) and 3-year overall survival rates were significantly superior among patients treated with S-1/docetaxel, compared with those treated with S-1 alone, commented lead study author Kazuhiro Yoshida, PhD, MD, director of Gifu University Hospital and professor and chairman of the department of surgical oncology, Gifu (Japan) University.

“The study met its primary endpoint and improved the RFS [recurrence-free survival],” he said. “Postoperative S-1 plus docetaxel was safe and manageable.”

Dr. Yoshida presented the updated findings of the GC-07 trial at the Gastrointestinal Cancers Symposium (GICS) 2021, which was held online this year.
 

S-1 widely used in Asia

S-1 is a novel oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine. The drug, which is a biochemical modulation of 5-fluorouracil, comprises tegafur and two types of enzyme inhibitor. It is widely used to treat various solid tumors in Asia.

“S1 is a standard postoperative adjuvant chemotherapy for patients with p-stage II/III gastric cancer in Asia,” said Dr. Yoshida, but the “outcome in p-stage III is unsatisfactory,” he added.

The GC-07 trial set out to further investigate the use of this drug in this patient population. Dr. Yoshida and colleagues included 915 patients with stage III gastric cancer who had undergone R0 resection and D2 lymphadenectomy and who tested negative on peritoneal-washing cytology. The patients were randomly assigned to receive either S-1 plus docetaxel or S-1 alone for up to 1 year in the postoperative setting.

The data presented at the meeting are the final results from GC-07. They confirm earlier data.

Previously, a second interim analysis showed that the trial had met its primary endpoint. As a result of that analysis, the study was terminated.

That interim analysis showed that the 3-year RFS of the S-1/docetaxel arm was significantly superior to that of the S-1 arm (65.9% vs. 49.6%; hazard ratio, 0.632; P = .0007).

Now, the final results, at a median follow-up of 48.2 months, show that there were 400 recurrences and 324 deaths. The 3-year RFS was 67.7% in the S-1/docetaxel group, which was significantly superior to the 57.4% reported in the S-1 group (HR, 0.715; P = .0008). Similarly, 3-year overall survival was 77.7% in the S-1/docetaxel group, vs. 71.2% in the S-1 group (HR, 0.742; P = .0076).

At 12 months, 62.7% of patients in the S-1 group had experienced treatment failure, compared with 56.2% in the combination-therapy group.

In addition to reducing overall relapse, treatment with combination therapy also decreased the incidence of relapse at specific sites, compared with S-1 alone. These included reductions in lymphatic recurrence (6.4% vs. 15.0%), hematogenous recurrence (9.7% vs. 15.5%), local recurrence (2.9% vs. 4.4%), and peritoneal recurrence (18.8% vs. 21.4%).

No new safety signals were observed, Dr. Yoshida commented. Grade 3/4 adverse events that occurred more frequently with S-1/docetaxel than with S-1 alone included neutropenia (39.2% vs. 16.4%), leukopenia (22.4% vs. 2.7%), and febrile neutropenia (5.7% vs. 0.4%).

However, the authors noted that, in a subgroup analysis, patients with stage IIIB disease did not derive the same benefit in RFS and overall survival with combination therapy as the patients with stage IIIA or IIIC disease.

The discussant for this paper, Rutika Mehta, MD, MPH, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., highlighted differences in benefit among the subgroups, as well as the finding that patients with stage IIIB appeared to benefit less.

However, she noted that the seventh edition of the American Joint Committee on Cancer TNM classification, which distinguishes patients on the basis of prognostic subgroups, is inaccurate for stage III disease, and this might have affected the study results. Dr. Mehta pointed to a previous analysis in which more than 33% of individuals with stage IIIB disease, determined in accordance with the seventh edition of the AJCC staging system, were reclassified as having stage IIIC disease, as determined using the more recent eighth edition.

“There were also few T2, N0, and N1 patients, making meaningful deductions in these subgroups not possible,” she said.

She said that despite these limitations, these “results are meaningful and impactful, and the combination of docetaxel and S-1 showed better RFS and overall survival than S-1 alone.

“These results do favor a new recommendation for the use of docetaxel plus S-1 for stage III gastric cancer patients after D2 lymphadenectomy,” she concluded.

The study was funded by the Japan Clinical Cancer Research Organization. Dr. Yoshida has received honoraria and research funding from many pharmaceutical companies, as listed in the abstract.

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