The Food and Drug Administration approved ritlecitinib on June 23 for the treatment of severe alopecia areata in people ages 12 and older, the manufacturer announced.

Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3). The recommended dose of ritlecitinib, which will be marketed as Litfulo, is 50 mg once a day, according to the statement announcing the approval from Pfizer.

Olivier Le Moal/Getty Images

It is the second JAK inhibitor approved for treating alopecia areata, following approval of baricitinib (Olumiant) in June 2022 for AA in adults. Ritlecitinib is the first JAK inhibitor approved for children ages 12 and older with AA.  

The European Medicines Agency has also accepted the Marketing Authorization Application for ritlecitinib in the same population and a decision is expected in the fourth quarter of this year.
 

Approval based on ALLEGRO trials

Approval was based on  previously announced results from trials, including the phase 2b/3 ALLEGRO study of ritlecitinib in 718 patients aged 12 years and older with alopecia areata, with 50% of more scalp hair loss, as measured by the Severity of Alopecia Tool (SALT), including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss).

Patients in the trial were experiencing a current episode of alopecia areata that had lasted between 6 months and 10 years. They were randomized to receive once-daily ritlecitinib at doses of 30 mg or 50 mg (with or without 1 month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg, or placebo.

Statistically significantly higher proportions of patients treated with ritlecitinib 30 mg and 50 mg (with or without the loading dose) had 80% or more scalp hair coverage, as measured by a SALT score of 20 or less after 6 months of treatment versus placebo. After 6 months of treatment, among those on the 50-mg dose, 23% had achieved a SALT score of 20 or less, compared with 2% of those on placebo. The results were published in The Lancet.

According to the company release, efficacy and safety of ritlecitinib was consistent between those ages 12-17 and adults, and the most common adverse events reported in the study, in at least 4% of patients treated with ritlecitinib, were headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and urticaria (4.6%). 

Ritlecitinib labeling includes the boxed warning about the risk for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, which is included in the labels for other JAK inhibitors.
 

Ritlecitinib evaluated for other diseases

In addition to alopecia areata, ritlecitinib has shown efficacy and acceptable safety in treating ulcerative colitis and is being evaluated for treating vitiligo, Crohn’s disease, and rheumatoid arthritis.

In the statement, the company says that ritlecitinib will be available “in the coming weeks.” The manufacturer says it also has completed regulatory submissions for ritlecitinib in the United Kingdom, China, and Japan, and expects decisions this year.

Alopecia areata affects about 6.8 million people in the United States and 147 million globally.

In a statement, Nicole Friedland, president and CEO of the National Alopecia Areata Foundation, said that NAAF “is thrilled to have a second FDA-approved treatment for alopecia areata, which is the first approved for adolescents.”

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

The Food and Drug Administration approved ritlecitinib on June 23 for the treatment of severe alopecia areata in people ages 12 and older, the manufacturer announced.

Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3). The recommended dose of ritlecitinib, which will be marketed as Litfulo, is 50 mg once a day, according to the statement announcing the approval from Pfizer.

Olivier Le Moal/Getty Images

It is the second JAK inhibitor approved for treating alopecia areata, following approval of baricitinib (Olumiant) in June 2022 for AA in adults. Ritlecitinib is the first JAK inhibitor approved for children ages 12 and older with AA.  

The European Medicines Agency has also accepted the Marketing Authorization Application for ritlecitinib in the same population and a decision is expected in the fourth quarter of this year.
 

Approval based on ALLEGRO trials

Approval was based on  previously announced results from trials, including the phase 2b/3 ALLEGRO study of ritlecitinib in 718 patients aged 12 years and older with alopecia areata, with 50% of more scalp hair loss, as measured by the Severity of Alopecia Tool (SALT), including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss).

Patients in the trial were experiencing a current episode of alopecia areata that had lasted between 6 months and 10 years. They were randomized to receive once-daily ritlecitinib at doses of 30 mg or 50 mg (with or without 1 month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg, or placebo.

Statistically significantly higher proportions of patients treated with ritlecitinib 30 mg and 50 mg (with or without the loading dose) had 80% or more scalp hair coverage, as measured by a SALT score of 20 or less after 6 months of treatment versus placebo. After 6 months of treatment, among those on the 50-mg dose, 23% had achieved a SALT score of 20 or less, compared with 2% of those on placebo. The results were published in The Lancet.

According to the company release, efficacy and safety of ritlecitinib was consistent between those ages 12-17 and adults, and the most common adverse events reported in the study, in at least 4% of patients treated with ritlecitinib, were headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and urticaria (4.6%). 

Ritlecitinib labeling includes the boxed warning about the risk for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, which is included in the labels for other JAK inhibitors.
 

Ritlecitinib evaluated for other diseases

In addition to alopecia areata, ritlecitinib has shown efficacy and acceptable safety in treating ulcerative colitis and is being evaluated for treating vitiligo, Crohn’s disease, and rheumatoid arthritis.

In the statement, the company says that ritlecitinib will be available “in the coming weeks.” The manufacturer says it also has completed regulatory submissions for ritlecitinib in the United Kingdom, China, and Japan, and expects decisions this year.

Alopecia areata affects about 6.8 million people in the United States and 147 million globally.

In a statement, Nicole Friedland, president and CEO of the National Alopecia Areata Foundation, said that NAAF “is thrilled to have a second FDA-approved treatment for alopecia areata, which is the first approved for adolescents.”

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

The Food and Drug Administration approved ritlecitinib on June 23 for the treatment of severe alopecia areata in people ages 12 and older, the manufacturer announced.

Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3). The recommended dose of ritlecitinib, which will be marketed as Litfulo, is 50 mg once a day, according to the statement announcing the approval from Pfizer.

Olivier Le Moal/Getty Images

It is the second JAK inhibitor approved for treating alopecia areata, following approval of baricitinib (Olumiant) in June 2022 for AA in adults. Ritlecitinib is the first JAK inhibitor approved for children ages 12 and older with AA.  

The European Medicines Agency has also accepted the Marketing Authorization Application for ritlecitinib in the same population and a decision is expected in the fourth quarter of this year.
 

Approval based on ALLEGRO trials

Approval was based on  previously announced results from trials, including the phase 2b/3 ALLEGRO study of ritlecitinib in 718 patients aged 12 years and older with alopecia areata, with 50% of more scalp hair loss, as measured by the Severity of Alopecia Tool (SALT), including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss).

Patients in the trial were experiencing a current episode of alopecia areata that had lasted between 6 months and 10 years. They were randomized to receive once-daily ritlecitinib at doses of 30 mg or 50 mg (with or without 1 month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg, or placebo.

Statistically significantly higher proportions of patients treated with ritlecitinib 30 mg and 50 mg (with or without the loading dose) had 80% or more scalp hair coverage, as measured by a SALT score of 20 or less after 6 months of treatment versus placebo. After 6 months of treatment, among those on the 50-mg dose, 23% had achieved a SALT score of 20 or less, compared with 2% of those on placebo. The results were published in The Lancet.

According to the company release, efficacy and safety of ritlecitinib was consistent between those ages 12-17 and adults, and the most common adverse events reported in the study, in at least 4% of patients treated with ritlecitinib, were headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and urticaria (4.6%). 

Ritlecitinib labeling includes the boxed warning about the risk for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, which is included in the labels for other JAK inhibitors.
 

Ritlecitinib evaluated for other diseases

In addition to alopecia areata, ritlecitinib has shown efficacy and acceptable safety in treating ulcerative colitis and is being evaluated for treating vitiligo, Crohn’s disease, and rheumatoid arthritis.

In the statement, the company says that ritlecitinib will be available “in the coming weeks.” The manufacturer says it also has completed regulatory submissions for ritlecitinib in the United Kingdom, China, and Japan, and expects decisions this year.

Alopecia areata affects about 6.8 million people in the United States and 147 million globally.

In a statement, Nicole Friedland, president and CEO of the National Alopecia Areata Foundation, said that NAAF “is thrilled to have a second FDA-approved treatment for alopecia areata, which is the first approved for adolescents.”

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

Background

Hodgkin lymphoma occurs in fewer than 9,000 individuals in the United States each year,¹ but it is one of the most common types of cancer in AYAs.² For the purposes of cHL, AYA is typically defined as an age range of 18 to 39 years, which covers the first of 2 bimodal peaks in incidence but stops short of the second.^3,4 The first of these peaks occurs between the ages of 15 and 34 years, while the second begins at about age 55.⁵ Children younger than 15 years of age can also develop Hodgkin lymphoma, but it is less common.⁶

In AYAs and in adults, more than 90% of patients with Hodgkin lymphoma have cHL.⁷ Most AYAs present with the nodular sclerosis subtype, but cHL is managed differently in pediatric patients versus in adult centers.^8,9 Evidence suggests that the specific risks of common treatment protocols, although similar, are not the same in AYAs as in adults.^10,11 Even though the literature evaluating the presentation and management of AYA cHL has been growing since 2005, when the AYA Oncology Progress Review Group called for AYAs to be recognized
as a distinct group, clinical trials specific to AYA cHL remain limited.⁹

Major Hodgkin lymphoma guidelines only partially address AYAs as a distinct group. In guidelines issued by the National Cancer Institute, the differences in clinical presentation of AYAs are described for young children, AYAs, and older adults, but there are no treatment recommendations specific to AYAs.¹² Guidelines from the EuroNet Paediatric Hodgkin Lymphoma Group offer recommendations for relapsed and refractory Hodgkin lymphoma, but do not differentiate between children and adolescents.¹³ The National Comprehensive Cancer Network (NCCN) provides separate treatment recommendations for patients 18 years or younger and those who are older than 18.^14,15 For Hodgkin lymphoma, AYA is not addressed as a separate category even though the NCCN has provided general guidelines for treatment of malignancies in AYA.¹⁶

First-line therapies are effective in children, AYAs, and adults. Survival rates at 5 years have increased steadily, approaching or exceeding 90% across age groups even for patients with unfavorable risk characteristics.¹⁷ This success has permitted greater focus on developing strategies that preserve efficacy with lower acute and long-term risks.

Risk-Adapted Therapies

While the potential for new and novel therapies to reduce the risk of long-term toxicities continues to be explored, adjusting existing regimens to reduce these risks has proven to be a viable strategy. This adjustment is a standard of care in the pediatric setting based on results from such studies as German GPOH-HD 95, which suggested that doses of radiotherapy, a major contributor to late toxicities,¹⁸ can be omitted in patients with a complete response after chemotherapy.¹¹ This pediatric trial contained both younger children and adolescents, but subsequent secondary analyses looking specifically at AYAs in this and other trials have suggested that efficacy is similarly preserved with risk-adapted strategies.⁹

However, due to AYA patients with cHL being treated using both pediatric and adult approaches, the persistent debate about optimal therapies in this age group complicates the effort to define a well-accepted strategy for risk adjustment. While risk-adapted strategies that rely on interim positron emission tomography (PET) to calibrate treatment intensity are now being used routinely across age stratifications, other initiatives are creating additional opportunities to gauge the impact on late effects in AYAs. These include strategies to improve collaboration across groups of trialists and data generated by observational cohorts, which can evaluate late effects not captured in time-limited clinical trials.

Among recent data supporting risk-adjusted therapy, the toxicity outcomes from a multicenter trial of PET-guided intensive treatment in patients with newly diagnosed advanced cHL were presented at the 2022 annual meeting of the American Society of Hematology.¹⁹ This phase 3 trial enrolled patients younger than 60 years, 79% of whom were younger than 45 years. Building on previous evidence that PET guidance improves the safety of eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), nearly 1,500 patients were randomized to this strategy or to PET-guided BrECADD, a modified eBEACOPP in which the antibody conjugate brentuximab vedotin (BV) was substituted for bleomycin. For an adjudicated endpoint of treatment-related morbidity, the experimental BrECAAD regimen reduced the risk by nearly 30% (hazard ratio [HR] 0.72). It is unclear whether this strategy will be used in the United States, where trials have been built on ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) rather than BEACOPP.

Efficacy data from this trial are not yet available, and these data will be important. There is concern that PET-directed therapy might result in lower toxicity at a cost of reduced rates of disease control. It is possible that the serious consequences of late toxicities—including infertility, compromised cardiovascular function, secondary cancers, and other organ damage—might need to be balanced against some loss of efficacy.

Novel Targeted Therapies

The goal of reducing late toxicities of cHL therapy in AYAs is also likely to be advanced by novel therapies. Research endeavors include a multicenter collaboration between US and Canadian investigators that is exploring the combination of nivolumab (a checkpoint inhibitor) plus BV.²⁰ The trial recently completed accrual and includes both adult and pediatric patients. If novel agents prove effective for improving efficacy while reducing the risk of late complications in AYAs, they are expected to have a profound effect on clinical practice.

Arguably, the era of targeted and novel therapies in cHL was initiated more than 10 years ago with the introduction of BV for the treatment of advanced disease in older adults.²¹ BV was moved into the front line for patients 18 years of age or older with advanced cHL in a trial that compared the standard of ABVD to the same drugs with BV substituted for bleomycin.²² In this study, the BV-containing regimen was associated with a significantly improved progression-free survival (PFS) (P = .04) and a lower rate of adverse events, including pulmonary toxicity (1% vs 3%) after 2 years of follow-up.

A similar study recently associated a BV-containing regimen with even greater efficacy in pediatric high-risk cHL.²³ In this multicenter study with 600 treatment-naïve patients ranging in age from 2 to 21 years, the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide was compared to the same regimen with BV substituted for bleomycin. With event-free survival as the primary endpoint, the experimental regimen was associated with a nearly 60% reduction in the risk of an adverse event or death (HR 0.41). However, no substantial differences were noted in toxicity after a follow-up of 42 months. It not yet clear whether the elimination of bleomycin will translate into less late toxicity, such as pulmonary or cardiovascular morbidity.

In the era of targeted therapies, the experience with BV has been a step toward more effective treatments using novel mechanisms of action to improve outcomes when used in the first-line treatment of patients with high-risk disease. Historically, many regimens and treatments that have demonstrated efficacy in relapsed and refractory cHL have found their way into the first-line setting. This trend might also be true of the checkpoint inhibitors, which have been tested extensively in relapsed/refractory cHL. In AYA patients with cHL, the rationale for these treatments might not only include a poor predicted response to current regimens, but a reduced risk of late toxicities if long-term follow-up demonstrates these treatments reduce late complications, such as secondary malignancies, which are associated with standard strategies, particularly those that include radiotherapy.

If targeted therapies do preserve efficacy and reduce risk of late complications, strategies to individualize therapy will remain relevant. Many of the emerging targeted therapies involve challenging and costly treatment protocols that demand selective application. Efforts to develop simpler and more precise biomarkers might streamline this task. Of promising developments in this area, cell-free DNA (cfDNA) appears to be near routine clinical application. A small study of cfDNA conducted in 121 patients found that minimal residual disease assessment by repeat cfDNA sequencing predicted response and PFS when performed as early as a week after treatment initiation.²⁴ If larger studies confirm accuracy, this biomarker strategy might prove simpler and more convenient than PET imaging.

Summary

In the treatment of hematologic malignancies, cHL is widely regarded as a success story with high rates of extended survival among children, AYAs, and older adults. This level of success does not obviate the need for even more effective treatments, and also permits more attention to be directed to reducing the risk of late toxicities. For the AYA population, which represents a large group with cHL, the current directions of clinical research offer the promise of imminent changes in how the disease is controlled and a reduction in treatment-related late morbidity and mortality.

Click to read more from 2023 Rare Diseases Report: Cancers

Background

Hodgkin lymphoma occurs in fewer than 9,000 individuals in the United States each year,¹ but it is one of the most common types of cancer in AYAs.² For the purposes of cHL, AYA is typically defined as an age range of 18 to 39 years, which covers the first of 2 bimodal peaks in incidence but stops short of the second.^3,4 The first of these peaks occurs between the ages of 15 and 34 years, while the second begins at about age 55.⁵ Children younger than 15 years of age can also develop Hodgkin lymphoma, but it is less common.⁶

In AYAs and in adults, more than 90% of patients with Hodgkin lymphoma have cHL.⁷ Most AYAs present with the nodular sclerosis subtype, but cHL is managed differently in pediatric patients versus in adult centers.^8,9 Evidence suggests that the specific risks of common treatment protocols, although similar, are not the same in AYAs as in adults.^10,11 Even though the literature evaluating the presentation and management of AYA cHL has been growing since 2005, when the AYA Oncology Progress Review Group called for AYAs to be recognized
as a distinct group, clinical trials specific to AYA cHL remain limited.⁹

Major Hodgkin lymphoma guidelines only partially address AYAs as a distinct group. In guidelines issued by the National Cancer Institute, the differences in clinical presentation of AYAs are described for young children, AYAs, and older adults, but there are no treatment recommendations specific to AYAs.¹² Guidelines from the EuroNet Paediatric Hodgkin Lymphoma Group offer recommendations for relapsed and refractory Hodgkin lymphoma, but do not differentiate between children and adolescents.¹³ The National Comprehensive Cancer Network (NCCN) provides separate treatment recommendations for patients 18 years or younger and those who are older than 18.^14,15 For Hodgkin lymphoma, AYA is not addressed as a separate category even though the NCCN has provided general guidelines for treatment of malignancies in AYA.¹⁶

First-line therapies are effective in children, AYAs, and adults. Survival rates at 5 years have increased steadily, approaching or exceeding 90% across age groups even for patients with unfavorable risk characteristics.¹⁷ This success has permitted greater focus on developing strategies that preserve efficacy with lower acute and long-term risks.

Risk-Adapted Therapies

While the potential for new and novel therapies to reduce the risk of long-term toxicities continues to be explored, adjusting existing regimens to reduce these risks has proven to be a viable strategy. This adjustment is a standard of care in the pediatric setting based on results from such studies as German GPOH-HD 95, which suggested that doses of radiotherapy, a major contributor to late toxicities,¹⁸ can be omitted in patients with a complete response after chemotherapy.¹¹ This pediatric trial contained both younger children and adolescents, but subsequent secondary analyses looking specifically at AYAs in this and other trials have suggested that efficacy is similarly preserved with risk-adapted strategies.⁹

However, due to AYA patients with cHL being treated using both pediatric and adult approaches, the persistent debate about optimal therapies in this age group complicates the effort to define a well-accepted strategy for risk adjustment. While risk-adapted strategies that rely on interim positron emission tomography (PET) to calibrate treatment intensity are now being used routinely across age stratifications, other initiatives are creating additional opportunities to gauge the impact on late effects in AYAs. These include strategies to improve collaboration across groups of trialists and data generated by observational cohorts, which can evaluate late effects not captured in time-limited clinical trials.

Among recent data supporting risk-adjusted therapy, the toxicity outcomes from a multicenter trial of PET-guided intensive treatment in patients with newly diagnosed advanced cHL were presented at the 2022 annual meeting of the American Society of Hematology.¹⁹ This phase 3 trial enrolled patients younger than 60 years, 79% of whom were younger than 45 years. Building on previous evidence that PET guidance improves the safety of eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), nearly 1,500 patients were randomized to this strategy or to PET-guided BrECADD, a modified eBEACOPP in which the antibody conjugate brentuximab vedotin (BV) was substituted for bleomycin. For an adjudicated endpoint of treatment-related morbidity, the experimental BrECAAD regimen reduced the risk by nearly 30% (hazard ratio [HR] 0.72). It is unclear whether this strategy will be used in the United States, where trials have been built on ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) rather than BEACOPP.

Efficacy data from this trial are not yet available, and these data will be important. There is concern that PET-directed therapy might result in lower toxicity at a cost of reduced rates of disease control. It is possible that the serious consequences of late toxicities—including infertility, compromised cardiovascular function, secondary cancers, and other organ damage—might need to be balanced against some loss of efficacy.

Novel Targeted Therapies

The goal of reducing late toxicities of cHL therapy in AYAs is also likely to be advanced by novel therapies. Research endeavors include a multicenter collaboration between US and Canadian investigators that is exploring the combination of nivolumab (a checkpoint inhibitor) plus BV.²⁰ The trial recently completed accrual and includes both adult and pediatric patients. If novel agents prove effective for improving efficacy while reducing the risk of late complications in AYAs, they are expected to have a profound effect on clinical practice.

Arguably, the era of targeted and novel therapies in cHL was initiated more than 10 years ago with the introduction of BV for the treatment of advanced disease in older adults.²¹ BV was moved into the front line for patients 18 years of age or older with advanced cHL in a trial that compared the standard of ABVD to the same drugs with BV substituted for bleomycin.²² In this study, the BV-containing regimen was associated with a significantly improved progression-free survival (PFS) (P = .04) and a lower rate of adverse events, including pulmonary toxicity (1% vs 3%) after 2 years of follow-up.

A similar study recently associated a BV-containing regimen with even greater efficacy in pediatric high-risk cHL.²³ In this multicenter study with 600 treatment-naïve patients ranging in age from 2 to 21 years, the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide was compared to the same regimen with BV substituted for bleomycin. With event-free survival as the primary endpoint, the experimental regimen was associated with a nearly 60% reduction in the risk of an adverse event or death (HR 0.41). However, no substantial differences were noted in toxicity after a follow-up of 42 months. It not yet clear whether the elimination of bleomycin will translate into less late toxicity, such as pulmonary or cardiovascular morbidity.

In the era of targeted therapies, the experience with BV has been a step toward more effective treatments using novel mechanisms of action to improve outcomes when used in the first-line treatment of patients with high-risk disease. Historically, many regimens and treatments that have demonstrated efficacy in relapsed and refractory cHL have found their way into the first-line setting. This trend might also be true of the checkpoint inhibitors, which have been tested extensively in relapsed/refractory cHL. In AYA patients with cHL, the rationale for these treatments might not only include a poor predicted response to current regimens, but a reduced risk of late toxicities if long-term follow-up demonstrates these treatments reduce late complications, such as secondary malignancies, which are associated with standard strategies, particularly those that include radiotherapy.

If targeted therapies do preserve efficacy and reduce risk of late complications, strategies to individualize therapy will remain relevant. Many of the emerging targeted therapies involve challenging and costly treatment protocols that demand selective application. Efforts to develop simpler and more precise biomarkers might streamline this task. Of promising developments in this area, cell-free DNA (cfDNA) appears to be near routine clinical application. A small study of cfDNA conducted in 121 patients found that minimal residual disease assessment by repeat cfDNA sequencing predicted response and PFS when performed as early as a week after treatment initiation.²⁴ If larger studies confirm accuracy, this biomarker strategy might prove simpler and more convenient than PET imaging.

Summary

In the treatment of hematologic malignancies, cHL is widely regarded as a success story with high rates of extended survival among children, AYAs, and older adults. This level of success does not obviate the need for even more effective treatments, and also permits more attention to be directed to reducing the risk of late toxicities. For the AYA population, which represents a large group with cHL, the current directions of clinical research offer the promise of imminent changes in how the disease is controlled and a reduction in treatment-related late morbidity and mortality.

Click to read more from 2023 Rare Diseases Report: Cancers

Background

Hodgkin lymphoma occurs in fewer than 9,000 individuals in the United States each year,¹ but it is one of the most common types of cancer in AYAs.² For the purposes of cHL, AYA is typically defined as an age range of 18 to 39 years, which covers the first of 2 bimodal peaks in incidence but stops short of the second.^3,4 The first of these peaks occurs between the ages of 15 and 34 years, while the second begins at about age 55.⁵ Children younger than 15 years of age can also develop Hodgkin lymphoma, but it is less common.⁶

In AYAs and in adults, more than 90% of patients with Hodgkin lymphoma have cHL.⁷ Most AYAs present with the nodular sclerosis subtype, but cHL is managed differently in pediatric patients versus in adult centers.^8,9 Evidence suggests that the specific risks of common treatment protocols, although similar, are not the same in AYAs as in adults.^10,11 Even though the literature evaluating the presentation and management of AYA cHL has been growing since 2005, when the AYA Oncology Progress Review Group called for AYAs to be recognized
as a distinct group, clinical trials specific to AYA cHL remain limited.⁹

Major Hodgkin lymphoma guidelines only partially address AYAs as a distinct group. In guidelines issued by the National Cancer Institute, the differences in clinical presentation of AYAs are described for young children, AYAs, and older adults, but there are no treatment recommendations specific to AYAs.¹² Guidelines from the EuroNet Paediatric Hodgkin Lymphoma Group offer recommendations for relapsed and refractory Hodgkin lymphoma, but do not differentiate between children and adolescents.¹³ The National Comprehensive Cancer Network (NCCN) provides separate treatment recommendations for patients 18 years or younger and those who are older than 18.^14,15 For Hodgkin lymphoma, AYA is not addressed as a separate category even though the NCCN has provided general guidelines for treatment of malignancies in AYA.¹⁶

First-line therapies are effective in children, AYAs, and adults. Survival rates at 5 years have increased steadily, approaching or exceeding 90% across age groups even for patients with unfavorable risk characteristics.¹⁷ This success has permitted greater focus on developing strategies that preserve efficacy with lower acute and long-term risks.

Risk-Adapted Therapies

While the potential for new and novel therapies to reduce the risk of long-term toxicities continues to be explored, adjusting existing regimens to reduce these risks has proven to be a viable strategy. This adjustment is a standard of care in the pediatric setting based on results from such studies as German GPOH-HD 95, which suggested that doses of radiotherapy, a major contributor to late toxicities,¹⁸ can be omitted in patients with a complete response after chemotherapy.¹¹ This pediatric trial contained both younger children and adolescents, but subsequent secondary analyses looking specifically at AYAs in this and other trials have suggested that efficacy is similarly preserved with risk-adapted strategies.⁹

However, due to AYA patients with cHL being treated using both pediatric and adult approaches, the persistent debate about optimal therapies in this age group complicates the effort to define a well-accepted strategy for risk adjustment. While risk-adapted strategies that rely on interim positron emission tomography (PET) to calibrate treatment intensity are now being used routinely across age stratifications, other initiatives are creating additional opportunities to gauge the impact on late effects in AYAs. These include strategies to improve collaboration across groups of trialists and data generated by observational cohorts, which can evaluate late effects not captured in time-limited clinical trials.

Among recent data supporting risk-adjusted therapy, the toxicity outcomes from a multicenter trial of PET-guided intensive treatment in patients with newly diagnosed advanced cHL were presented at the 2022 annual meeting of the American Society of Hematology.¹⁹ This phase 3 trial enrolled patients younger than 60 years, 79% of whom were younger than 45 years. Building on previous evidence that PET guidance improves the safety of eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), nearly 1,500 patients were randomized to this strategy or to PET-guided BrECADD, a modified eBEACOPP in which the antibody conjugate brentuximab vedotin (BV) was substituted for bleomycin. For an adjudicated endpoint of treatment-related morbidity, the experimental BrECAAD regimen reduced the risk by nearly 30% (hazard ratio [HR] 0.72). It is unclear whether this strategy will be used in the United States, where trials have been built on ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) rather than BEACOPP.

Efficacy data from this trial are not yet available, and these data will be important. There is concern that PET-directed therapy might result in lower toxicity at a cost of reduced rates of disease control. It is possible that the serious consequences of late toxicities—including infertility, compromised cardiovascular function, secondary cancers, and other organ damage—might need to be balanced against some loss of efficacy.

Novel Targeted Therapies

The goal of reducing late toxicities of cHL therapy in AYAs is also likely to be advanced by novel therapies. Research endeavors include a multicenter collaboration between US and Canadian investigators that is exploring the combination of nivolumab (a checkpoint inhibitor) plus BV.²⁰ The trial recently completed accrual and includes both adult and pediatric patients. If novel agents prove effective for improving efficacy while reducing the risk of late complications in AYAs, they are expected to have a profound effect on clinical practice.

Arguably, the era of targeted and novel therapies in cHL was initiated more than 10 years ago with the introduction of BV for the treatment of advanced disease in older adults.²¹ BV was moved into the front line for patients 18 years of age or older with advanced cHL in a trial that compared the standard of ABVD to the same drugs with BV substituted for bleomycin.²² In this study, the BV-containing regimen was associated with a significantly improved progression-free survival (PFS) (P = .04) and a lower rate of adverse events, including pulmonary toxicity (1% vs 3%) after 2 years of follow-up.

A similar study recently associated a BV-containing regimen with even greater efficacy in pediatric high-risk cHL.²³ In this multicenter study with 600 treatment-naïve patients ranging in age from 2 to 21 years, the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide was compared to the same regimen with BV substituted for bleomycin. With event-free survival as the primary endpoint, the experimental regimen was associated with a nearly 60% reduction in the risk of an adverse event or death (HR 0.41). However, no substantial differences were noted in toxicity after a follow-up of 42 months. It not yet clear whether the elimination of bleomycin will translate into less late toxicity, such as pulmonary or cardiovascular morbidity.

In the era of targeted therapies, the experience with BV has been a step toward more effective treatments using novel mechanisms of action to improve outcomes when used in the first-line treatment of patients with high-risk disease. Historically, many regimens and treatments that have demonstrated efficacy in relapsed and refractory cHL have found their way into the first-line setting. This trend might also be true of the checkpoint inhibitors, which have been tested extensively in relapsed/refractory cHL. In AYA patients with cHL, the rationale for these treatments might not only include a poor predicted response to current regimens, but a reduced risk of late toxicities if long-term follow-up demonstrates these treatments reduce late complications, such as secondary malignancies, which are associated with standard strategies, particularly those that include radiotherapy.

If targeted therapies do preserve efficacy and reduce risk of late complications, strategies to individualize therapy will remain relevant. Many of the emerging targeted therapies involve challenging and costly treatment protocols that demand selective application. Efforts to develop simpler and more precise biomarkers might streamline this task. Of promising developments in this area, cell-free DNA (cfDNA) appears to be near routine clinical application. A small study of cfDNA conducted in 121 patients found that minimal residual disease assessment by repeat cfDNA sequencing predicted response and PFS when performed as early as a week after treatment initiation.²⁴ If larger studies confirm accuracy, this biomarker strategy might prove simpler and more convenient than PET imaging.

Summary

In the treatment of hematologic malignancies, cHL is widely regarded as a success story with high rates of extended survival among children, AYAs, and older adults. This level of success does not obviate the need for even more effective treatments, and also permits more attention to be directed to reducing the risk of late toxicities. For the AYA population, which represents a large group with cHL, the current directions of clinical research offer the promise of imminent changes in how the disease is controlled and a reduction in treatment-related late morbidity and mortality.

Click to read more from 2023 Rare Diseases Report: Cancers

Controversies remain in treating inguinal hernias in children and the American Academy of Pediatrics is addressing them with a clinical report.

Faraz A. Khan, MD, an adjunct associate professor in the division of pediatric surgery at Loma Linda (Calif.) University Children’s Hospital, led the AAP’s Committee on Fetus and Newborn, sections on surgery and urology, in writing the guidance, published in Pediatrics.

An inguinal hernia, a common pediatric surgical condition (90% are in boys, the authors wrote), appears as a bulge in the groin or scrotum and requires surgical repair to prevent a more severe incarcerated hernia, which occurs when organs from the abdomen become trapped in the hernia.

The risk of that incarceration drives the preference and timing of surgical repair, the authors wrote.

The incidence of inguinal hernias is about 8-50 per 1,000 live births in term infants and is much higher in extremely low-birth-weight infants.

Ankush Gosain, MD, PhD, chief of pediatric surgery at Children’s Hospital Colorado, Aurora, who was not involved in the AAP clinical report, said in an interview that the best timing for the surgery on a premature infant has been an unanswered question and this guidance is helpful.

Inguinal hernias in preterm infants are especially common. The incidence is reported to be as high as 20%.

Repair can wait until babies have left NICU

The authors concluded that there was moderate-quality evidence supporting deferring hernia repair until after discharge from the neonatal intensive care unit because this may reduce the risk of respiratory problems without increasing risk of incarceration or another operation.

But Dr. Gosain noted that the authors left the door open for data from a study that recently finished enrolling patients. That trial (Dr. Gosain is a site investigator) is expected to help determine whether an early- or late-term approach is best in preterm infants.

“There are pluses and minuses that we and the neonatologists and the anesthesiologists recognize,” he said.
 

Laparoscopic approach as good, sometimes better

Dr. Gosain also said he was glad to see the authors addressed the merits of the laparoscopic approach and when it is preferred.

The authors noted that a laparoscopic approach is increasingly popular – rates have grown fivefold between 2009 and 2018 – and they found it is “at least as effective as, if not better than,” the current preferred method, traditional open high ligation of the hernia sac.

Laparoscopy also appears to be a feasible option in managing recurrent hernias.

Dr. Gosain said that, when the laparoscopic approach was developed, there was concern that it would lead to higher recurrence of the hernias. “That concern has diminished over time,” he added. The paper helps give surgeons and pediatricians peace of mind that this is a safe approach.
 

Who should perform the surgeries?

The authors concluded that, ideally, pediatric surgical specialists, pediatric urologists, or general surgeons with a significant yearly case volume should perform the surgeries.

They found a significant inverse relationship between recurrence rates and general surgeon case volume: general surgeons who completed fewer than 10 pediatric inguinal hernias per year had the highest recurrence rates and the highest-volume general surgeons had recurrence rates similar to pediatric surgical specialists.

Pediatric surgical specialists trained in fellowships had the lowest rate of hernia recurrences.

Dr. Gosain said he was glad the authors pointed out that both the surgeon and the anesthesiologist ideally should have that specialty training.
 

No evidence that anesthetic exposure affects neurodevelopment

The researchers found no conclusive evidence that otherwise-healthy children’s exposure to a single relatively short duration of anesthetic adds any significant risk to neurodevelopment or academic performance, or increases risk of ADHD or autism spectrum disorder.

Contralateral exploration with unilateral hernia

Providers continue to debate contralateral exploration among patients with unilateral inguinal hernia. Proponents of exploration cite a 10%-15% rate of developing of a hernia at a later time. Therefore, routine exploration and, if identified, ligation of a patent processus vaginalis (PPV) may avoid a subsequent anesthetic.

Opponents counter that not all PPVs will become clinically significant inguinal hernias, and doing routine exploration exposes the patient to potentially unnecessary complications.

The authors wrote: “In the absence of strong data for or against repair of incidentally discovered contralateral PPV, family values related to the risks and benefits of each approach from a nuanced preoperative discussion should be considered.”

Dr. Gosain said that, with all of the guidance points, “you need to have a true conversation between the surgeon and the parents with pluses and minuses of the different approaches because one is not necessarily absolutely better than the other.”

The authors and Dr. Gosain declare no relevant financial relationships.

Controversies remain in treating inguinal hernias in children and the American Academy of Pediatrics is addressing them with a clinical report.

Faraz A. Khan, MD, an adjunct associate professor in the division of pediatric surgery at Loma Linda (Calif.) University Children’s Hospital, led the AAP’s Committee on Fetus and Newborn, sections on surgery and urology, in writing the guidance, published in Pediatrics.

An inguinal hernia, a common pediatric surgical condition (90% are in boys, the authors wrote), appears as a bulge in the groin or scrotum and requires surgical repair to prevent a more severe incarcerated hernia, which occurs when organs from the abdomen become trapped in the hernia.

The risk of that incarceration drives the preference and timing of surgical repair, the authors wrote.

The incidence of inguinal hernias is about 8-50 per 1,000 live births in term infants and is much higher in extremely low-birth-weight infants.

Ankush Gosain, MD, PhD, chief of pediatric surgery at Children’s Hospital Colorado, Aurora, who was not involved in the AAP clinical report, said in an interview that the best timing for the surgery on a premature infant has been an unanswered question and this guidance is helpful.

Inguinal hernias in preterm infants are especially common. The incidence is reported to be as high as 20%.

Repair can wait until babies have left NICU

The authors concluded that there was moderate-quality evidence supporting deferring hernia repair until after discharge from the neonatal intensive care unit because this may reduce the risk of respiratory problems without increasing risk of incarceration or another operation.

But Dr. Gosain noted that the authors left the door open for data from a study that recently finished enrolling patients. That trial (Dr. Gosain is a site investigator) is expected to help determine whether an early- or late-term approach is best in preterm infants.

“There are pluses and minuses that we and the neonatologists and the anesthesiologists recognize,” he said.
 

Laparoscopic approach as good, sometimes better

Dr. Gosain also said he was glad to see the authors addressed the merits of the laparoscopic approach and when it is preferred.

The authors noted that a laparoscopic approach is increasingly popular – rates have grown fivefold between 2009 and 2018 – and they found it is “at least as effective as, if not better than,” the current preferred method, traditional open high ligation of the hernia sac.

Laparoscopy also appears to be a feasible option in managing recurrent hernias.

Dr. Gosain said that, when the laparoscopic approach was developed, there was concern that it would lead to higher recurrence of the hernias. “That concern has diminished over time,” he added. The paper helps give surgeons and pediatricians peace of mind that this is a safe approach.
 

Who should perform the surgeries?

The authors concluded that, ideally, pediatric surgical specialists, pediatric urologists, or general surgeons with a significant yearly case volume should perform the surgeries.

They found a significant inverse relationship between recurrence rates and general surgeon case volume: general surgeons who completed fewer than 10 pediatric inguinal hernias per year had the highest recurrence rates and the highest-volume general surgeons had recurrence rates similar to pediatric surgical specialists.

Pediatric surgical specialists trained in fellowships had the lowest rate of hernia recurrences.

Dr. Gosain said he was glad the authors pointed out that both the surgeon and the anesthesiologist ideally should have that specialty training.
 

No evidence that anesthetic exposure affects neurodevelopment

The researchers found no conclusive evidence that otherwise-healthy children’s exposure to a single relatively short duration of anesthetic adds any significant risk to neurodevelopment or academic performance, or increases risk of ADHD or autism spectrum disorder.

Contralateral exploration with unilateral hernia

Providers continue to debate contralateral exploration among patients with unilateral inguinal hernia. Proponents of exploration cite a 10%-15% rate of developing of a hernia at a later time. Therefore, routine exploration and, if identified, ligation of a patent processus vaginalis (PPV) may avoid a subsequent anesthetic.

Opponents counter that not all PPVs will become clinically significant inguinal hernias, and doing routine exploration exposes the patient to potentially unnecessary complications.

The authors wrote: “In the absence of strong data for or against repair of incidentally discovered contralateral PPV, family values related to the risks and benefits of each approach from a nuanced preoperative discussion should be considered.”

Dr. Gosain said that, with all of the guidance points, “you need to have a true conversation between the surgeon and the parents with pluses and minuses of the different approaches because one is not necessarily absolutely better than the other.”

The authors and Dr. Gosain declare no relevant financial relationships.

Controversies remain in treating inguinal hernias in children and the American Academy of Pediatrics is addressing them with a clinical report.

Faraz A. Khan, MD, an adjunct associate professor in the division of pediatric surgery at Loma Linda (Calif.) University Children’s Hospital, led the AAP’s Committee on Fetus and Newborn, sections on surgery and urology, in writing the guidance, published in Pediatrics.

An inguinal hernia, a common pediatric surgical condition (90% are in boys, the authors wrote), appears as a bulge in the groin or scrotum and requires surgical repair to prevent a more severe incarcerated hernia, which occurs when organs from the abdomen become trapped in the hernia.

The risk of that incarceration drives the preference and timing of surgical repair, the authors wrote.

The incidence of inguinal hernias is about 8-50 per 1,000 live births in term infants and is much higher in extremely low-birth-weight infants.

Ankush Gosain, MD, PhD, chief of pediatric surgery at Children’s Hospital Colorado, Aurora, who was not involved in the AAP clinical report, said in an interview that the best timing for the surgery on a premature infant has been an unanswered question and this guidance is helpful.

Inguinal hernias in preterm infants are especially common. The incidence is reported to be as high as 20%.

Repair can wait until babies have left NICU

The authors concluded that there was moderate-quality evidence supporting deferring hernia repair until after discharge from the neonatal intensive care unit because this may reduce the risk of respiratory problems without increasing risk of incarceration or another operation.

But Dr. Gosain noted that the authors left the door open for data from a study that recently finished enrolling patients. That trial (Dr. Gosain is a site investigator) is expected to help determine whether an early- or late-term approach is best in preterm infants.

“There are pluses and minuses that we and the neonatologists and the anesthesiologists recognize,” he said.
 

Laparoscopic approach as good, sometimes better

Dr. Gosain also said he was glad to see the authors addressed the merits of the laparoscopic approach and when it is preferred.

The authors noted that a laparoscopic approach is increasingly popular – rates have grown fivefold between 2009 and 2018 – and they found it is “at least as effective as, if not better than,” the current preferred method, traditional open high ligation of the hernia sac.

Laparoscopy also appears to be a feasible option in managing recurrent hernias.

Dr. Gosain said that, when the laparoscopic approach was developed, there was concern that it would lead to higher recurrence of the hernias. “That concern has diminished over time,” he added. The paper helps give surgeons and pediatricians peace of mind that this is a safe approach.
 

Who should perform the surgeries?

The authors concluded that, ideally, pediatric surgical specialists, pediatric urologists, or general surgeons with a significant yearly case volume should perform the surgeries.

They found a significant inverse relationship between recurrence rates and general surgeon case volume: general surgeons who completed fewer than 10 pediatric inguinal hernias per year had the highest recurrence rates and the highest-volume general surgeons had recurrence rates similar to pediatric surgical specialists.

Pediatric surgical specialists trained in fellowships had the lowest rate of hernia recurrences.

Dr. Gosain said he was glad the authors pointed out that both the surgeon and the anesthesiologist ideally should have that specialty training.
 

No evidence that anesthetic exposure affects neurodevelopment

The researchers found no conclusive evidence that otherwise-healthy children’s exposure to a single relatively short duration of anesthetic adds any significant risk to neurodevelopment or academic performance, or increases risk of ADHD or autism spectrum disorder.

Contralateral exploration with unilateral hernia

Providers continue to debate contralateral exploration among patients with unilateral inguinal hernia. Proponents of exploration cite a 10%-15% rate of developing of a hernia at a later time. Therefore, routine exploration and, if identified, ligation of a patent processus vaginalis (PPV) may avoid a subsequent anesthetic.

Opponents counter that not all PPVs will become clinically significant inguinal hernias, and doing routine exploration exposes the patient to potentially unnecessary complications.

The authors wrote: “In the absence of strong data for or against repair of incidentally discovered contralateral PPV, family values related to the risks and benefits of each approach from a nuanced preoperative discussion should be considered.”

Dr. Gosain said that, with all of the guidance points, “you need to have a true conversation between the surgeon and the parents with pluses and minuses of the different approaches because one is not necessarily absolutely better than the other.”

The authors and Dr. Gosain declare no relevant financial relationships.

Patients with high- and very-high-risk cutaneous squamous cell carcinoma (CSCC), as defined by the 2022 National Comprehensive Cancer Network guidelines, have a significantly increased risk of developing local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and dying from the disease, according to new findings.

In addition, regardless of the NCCN risk group, the study found that Mohs surgery or peripheral and deep en face margin assessment (PDEMA) conferred a lower risk of developing LR, DM, and disease-related death.

“Although the NCCN included this new high-risk group in the last iteration of the guidelines, there were no studies that identified whether the high-risk group achieved the goal of identifying riskier tumors,” said senior author Emily Ruiz, MD, MPH, associate physician at the Mohs and Dermatologic Surgery Center at Brigham and Women’s Faulkner Hospital, Boston. “Based on the data in our study, the risk groups did risk stratify tumors and so clinicians can utilize the high-risk group risk factors to identify which tumors may require additional surveillance or treatment.”

The study was published online in JAMA Dermatology.

Most patients with CSCC are successfully treated with Mohs micrographic surgery or wide local excision (WLE) alone, but a subset will experience more severe and aggressive disease. While useful for prognostication, current staging systems do not incorporate patient factors or other high-risk tumor features that influence outcomes, which led to the NCCN reclassifying CSCC into low-, high-, and very high-risk groups. The NCCN guidelines also made a new recommendation that Mohs or PDEMA be the preferred method for tissue processing for high- and very-high-risk tumors, based on this new stratification.

However, these changes to the NCCN guidelines have not been validated. The goal of this study was to compare outcomes in very-high-, high-, and low-risk NCCN groups as well as comparing outcomes of CSCCs stratified by Mohs and WLE.

Dr. Ruiz and colleagues conducted a retrospective cohort study using patient data from two tertiary care academic medical centers. Their analysis included 10,196 tumors from 8,727 patients that were then stratified into low-risk (3,054 tumors [30.0%]), high-risk (6,269 tumors [61.5%]), and very-high-risk (873 tumors [8.6%]) groups.

Tumors in the very-high-risk group were more likely to have high-risk tumor and histologic features, such as large-caliber perineural invasion, large diameter, invasion beyond the subcutaneous fat or bone, poor differentiation, and lymphovascular invasion.

The authors found that, compared with the low-risk group, the high- and very-high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio, 1.99; P = .007; very-high-risk SHR, 12.66; P < .001); NM (high-risk SHR, 4.26; P = .02; very-high-risk SHR, 62.98; P < .001); DM (high-risk SHR, 2.2 × 10^7;P < .001; very-high-risk SHR, 6.3 × 10^8;P < .001); and DSD (high-risk SHR, 4.02; P = .03; very-high-risk SHR, 93.87; P < .001).

Adjusted 5-year cumulative incidence was also significantly higher in very-high- vs. high- and low-risk groups for all endpoints.

They next compared the procedures used to treat the tumors. Compared with WLE, patients treated with Mohs or PDEMA had a lower risk of LR (SHR, 0.65; P = .009), DM (SHR, 0.38; P = .02), and DSD (SHR, 0.55; P = .006).

Mohs and PDEMA have already became preferred surgical modalities for high- and very-high-risk tumors, and Dr. Ruiz pointed out that their analysis was for the entire cohort.

“We did not stratify this by risk group,” she said. “So our results do not change anything clinically at this time, but support prior studies that have found Mohs/PDEMA to have improved outcomes, compared to WLE. Further studies are needed evaluating surgical approach by risk-group.”

However, she emphasized, “our studies further validate prior evidence showing Mohs/PDEMA to have the lowest rates of recurrence and in this study, even disease-related death.”

Approached for an independent comment, Jeffrey M. Farma, MD, codirector of the melanoma and skin cancer program, and interim chair, department of surgical oncology, Fox Chase Cancer Center, Philadelphia, noted that this study supports the new reclassification of CSCC tumors by the NCCN, and confirms that the high-risk and very-high-risk tumors surely have a higher propensity for worse outcomes overall.

“That being said, the notion for type of resection and margin assessment is still an area of controversy in the dermatology, surgical oncology, and pathology community,” said Dr. Farma, who is also on the NCCN panel. “I believe we need further studies to truly understand the role of the type of resection and the pathologic evaluation play in this disease process.”

He also pointed out that it is unclear in this dataset if patients initially had any imaging to evaluate for local or regional metastatic disease. “It would be helpful to have a further understanding of which type of provider was performing the excisions, the type of excision decided upon, and if there was a standardized approach to [decide] which patients had MOHS or PDEMA and what was the surveillance for these patients both with imaging and physical examinations,” said Dr. Farma. “This data also evaluated patients over a long time period where practice patterns have evolved.”

Finally, he noted that the number of local and metastatic events subjectively seems low in this cohort. “We also do not know any information about the initial workup of the patients, patterns of recurrence, and adjuvant or palliative treatment after recurrence,” he added. “It is unclear from this manuscript how the type of resection or pathologic evaluation of margins leads to improved outcomes and further prospective studies are warranted.”

Dr. Ruiz reports reported serving as a coinvestigator and principal investigator for Regeneron Pharmaceuticals and as a coinvestigator for Merck and consulting for Checkpoint Therapeutics, BDO, and Genentech outside the submitted work. Dr. Farma has no disclosures other than the NCCN panel. The study was supported by Harvard Catalyst and the Harvard University Clinical and Translational Science Center and by Harvard University and its affiliated academic health care centers and partially supported by the Melvin Markey Discovery Fund at Cleveland Clinic Foundation.

Patients with high- and very-high-risk cutaneous squamous cell carcinoma (CSCC), as defined by the 2022 National Comprehensive Cancer Network guidelines, have a significantly increased risk of developing local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and dying from the disease, according to new findings.

In addition, regardless of the NCCN risk group, the study found that Mohs surgery or peripheral and deep en face margin assessment (PDEMA) conferred a lower risk of developing LR, DM, and disease-related death.

“Although the NCCN included this new high-risk group in the last iteration of the guidelines, there were no studies that identified whether the high-risk group achieved the goal of identifying riskier tumors,” said senior author Emily Ruiz, MD, MPH, associate physician at the Mohs and Dermatologic Surgery Center at Brigham and Women’s Faulkner Hospital, Boston. “Based on the data in our study, the risk groups did risk stratify tumors and so clinicians can utilize the high-risk group risk factors to identify which tumors may require additional surveillance or treatment.”

The study was published online in JAMA Dermatology.

Most patients with CSCC are successfully treated with Mohs micrographic surgery or wide local excision (WLE) alone, but a subset will experience more severe and aggressive disease. While useful for prognostication, current staging systems do not incorporate patient factors or other high-risk tumor features that influence outcomes, which led to the NCCN reclassifying CSCC into low-, high-, and very high-risk groups. The NCCN guidelines also made a new recommendation that Mohs or PDEMA be the preferred method for tissue processing for high- and very-high-risk tumors, based on this new stratification.

However, these changes to the NCCN guidelines have not been validated. The goal of this study was to compare outcomes in very-high-, high-, and low-risk NCCN groups as well as comparing outcomes of CSCCs stratified by Mohs and WLE.

Dr. Ruiz and colleagues conducted a retrospective cohort study using patient data from two tertiary care academic medical centers. Their analysis included 10,196 tumors from 8,727 patients that were then stratified into low-risk (3,054 tumors [30.0%]), high-risk (6,269 tumors [61.5%]), and very-high-risk (873 tumors [8.6%]) groups.

Tumors in the very-high-risk group were more likely to have high-risk tumor and histologic features, such as large-caliber perineural invasion, large diameter, invasion beyond the subcutaneous fat or bone, poor differentiation, and lymphovascular invasion.

The authors found that, compared with the low-risk group, the high- and very-high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio, 1.99; P = .007; very-high-risk SHR, 12.66; P < .001); NM (high-risk SHR, 4.26; P = .02; very-high-risk SHR, 62.98; P < .001); DM (high-risk SHR, 2.2 × 10^7;P < .001; very-high-risk SHR, 6.3 × 10^8;P < .001); and DSD (high-risk SHR, 4.02; P = .03; very-high-risk SHR, 93.87; P < .001).

Adjusted 5-year cumulative incidence was also significantly higher in very-high- vs. high- and low-risk groups for all endpoints.

They next compared the procedures used to treat the tumors. Compared with WLE, patients treated with Mohs or PDEMA had a lower risk of LR (SHR, 0.65; P = .009), DM (SHR, 0.38; P = .02), and DSD (SHR, 0.55; P = .006).

Mohs and PDEMA have already became preferred surgical modalities for high- and very-high-risk tumors, and Dr. Ruiz pointed out that their analysis was for the entire cohort.

“We did not stratify this by risk group,” she said. “So our results do not change anything clinically at this time, but support prior studies that have found Mohs/PDEMA to have improved outcomes, compared to WLE. Further studies are needed evaluating surgical approach by risk-group.”

However, she emphasized, “our studies further validate prior evidence showing Mohs/PDEMA to have the lowest rates of recurrence and in this study, even disease-related death.”

Approached for an independent comment, Jeffrey M. Farma, MD, codirector of the melanoma and skin cancer program, and interim chair, department of surgical oncology, Fox Chase Cancer Center, Philadelphia, noted that this study supports the new reclassification of CSCC tumors by the NCCN, and confirms that the high-risk and very-high-risk tumors surely have a higher propensity for worse outcomes overall.

“That being said, the notion for type of resection and margin assessment is still an area of controversy in the dermatology, surgical oncology, and pathology community,” said Dr. Farma, who is also on the NCCN panel. “I believe we need further studies to truly understand the role of the type of resection and the pathologic evaluation play in this disease process.”

He also pointed out that it is unclear in this dataset if patients initially had any imaging to evaluate for local or regional metastatic disease. “It would be helpful to have a further understanding of which type of provider was performing the excisions, the type of excision decided upon, and if there was a standardized approach to [decide] which patients had MOHS or PDEMA and what was the surveillance for these patients both with imaging and physical examinations,” said Dr. Farma. “This data also evaluated patients over a long time period where practice patterns have evolved.”

Finally, he noted that the number of local and metastatic events subjectively seems low in this cohort. “We also do not know any information about the initial workup of the patients, patterns of recurrence, and adjuvant or palliative treatment after recurrence,” he added. “It is unclear from this manuscript how the type of resection or pathologic evaluation of margins leads to improved outcomes and further prospective studies are warranted.”

Dr. Ruiz reports reported serving as a coinvestigator and principal investigator for Regeneron Pharmaceuticals and as a coinvestigator for Merck and consulting for Checkpoint Therapeutics, BDO, and Genentech outside the submitted work. Dr. Farma has no disclosures other than the NCCN panel. The study was supported by Harvard Catalyst and the Harvard University Clinical and Translational Science Center and by Harvard University and its affiliated academic health care centers and partially supported by the Melvin Markey Discovery Fund at Cleveland Clinic Foundation.

Patients with high- and very-high-risk cutaneous squamous cell carcinoma (CSCC), as defined by the 2022 National Comprehensive Cancer Network guidelines, have a significantly increased risk of developing local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and dying from the disease, according to new findings.

In addition, regardless of the NCCN risk group, the study found that Mohs surgery or peripheral and deep en face margin assessment (PDEMA) conferred a lower risk of developing LR, DM, and disease-related death.

“Although the NCCN included this new high-risk group in the last iteration of the guidelines, there were no studies that identified whether the high-risk group achieved the goal of identifying riskier tumors,” said senior author Emily Ruiz, MD, MPH, associate physician at the Mohs and Dermatologic Surgery Center at Brigham and Women’s Faulkner Hospital, Boston. “Based on the data in our study, the risk groups did risk stratify tumors and so clinicians can utilize the high-risk group risk factors to identify which tumors may require additional surveillance or treatment.”

The study was published online in JAMA Dermatology.

Most patients with CSCC are successfully treated with Mohs micrographic surgery or wide local excision (WLE) alone, but a subset will experience more severe and aggressive disease. While useful for prognostication, current staging systems do not incorporate patient factors or other high-risk tumor features that influence outcomes, which led to the NCCN reclassifying CSCC into low-, high-, and very high-risk groups. The NCCN guidelines also made a new recommendation that Mohs or PDEMA be the preferred method for tissue processing for high- and very-high-risk tumors, based on this new stratification.

However, these changes to the NCCN guidelines have not been validated. The goal of this study was to compare outcomes in very-high-, high-, and low-risk NCCN groups as well as comparing outcomes of CSCCs stratified by Mohs and WLE.

Dr. Ruiz and colleagues conducted a retrospective cohort study using patient data from two tertiary care academic medical centers. Their analysis included 10,196 tumors from 8,727 patients that were then stratified into low-risk (3,054 tumors [30.0%]), high-risk (6,269 tumors [61.5%]), and very-high-risk (873 tumors [8.6%]) groups.

Tumors in the very-high-risk group were more likely to have high-risk tumor and histologic features, such as large-caliber perineural invasion, large diameter, invasion beyond the subcutaneous fat or bone, poor differentiation, and lymphovascular invasion.

The authors found that, compared with the low-risk group, the high- and very-high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio, 1.99; P = .007; very-high-risk SHR, 12.66; P < .001); NM (high-risk SHR, 4.26; P = .02; very-high-risk SHR, 62.98; P < .001); DM (high-risk SHR, 2.2 × 10^7;P < .001; very-high-risk SHR, 6.3 × 10^8;P < .001); and DSD (high-risk SHR, 4.02; P = .03; very-high-risk SHR, 93.87; P < .001).

Adjusted 5-year cumulative incidence was also significantly higher in very-high- vs. high- and low-risk groups for all endpoints.

They next compared the procedures used to treat the tumors. Compared with WLE, patients treated with Mohs or PDEMA had a lower risk of LR (SHR, 0.65; P = .009), DM (SHR, 0.38; P = .02), and DSD (SHR, 0.55; P = .006).

Mohs and PDEMA have already became preferred surgical modalities for high- and very-high-risk tumors, and Dr. Ruiz pointed out that their analysis was for the entire cohort.

“We did not stratify this by risk group,” she said. “So our results do not change anything clinically at this time, but support prior studies that have found Mohs/PDEMA to have improved outcomes, compared to WLE. Further studies are needed evaluating surgical approach by risk-group.”

However, she emphasized, “our studies further validate prior evidence showing Mohs/PDEMA to have the lowest rates of recurrence and in this study, even disease-related death.”

Approached for an independent comment, Jeffrey M. Farma, MD, codirector of the melanoma and skin cancer program, and interim chair, department of surgical oncology, Fox Chase Cancer Center, Philadelphia, noted that this study supports the new reclassification of CSCC tumors by the NCCN, and confirms that the high-risk and very-high-risk tumors surely have a higher propensity for worse outcomes overall.

“That being said, the notion for type of resection and margin assessment is still an area of controversy in the dermatology, surgical oncology, and pathology community,” said Dr. Farma, who is also on the NCCN panel. “I believe we need further studies to truly understand the role of the type of resection and the pathologic evaluation play in this disease process.”

He also pointed out that it is unclear in this dataset if patients initially had any imaging to evaluate for local or regional metastatic disease. “It would be helpful to have a further understanding of which type of provider was performing the excisions, the type of excision decided upon, and if there was a standardized approach to [decide] which patients had MOHS or PDEMA and what was the surveillance for these patients both with imaging and physical examinations,” said Dr. Farma. “This data also evaluated patients over a long time period where practice patterns have evolved.”

Finally, he noted that the number of local and metastatic events subjectively seems low in this cohort. “We also do not know any information about the initial workup of the patients, patterns of recurrence, and adjuvant or palliative treatment after recurrence,” he added. “It is unclear from this manuscript how the type of resection or pathologic evaluation of margins leads to improved outcomes and further prospective studies are warranted.”

Dr. Ruiz reports reported serving as a coinvestigator and principal investigator for Regeneron Pharmaceuticals and as a coinvestigator for Merck and consulting for Checkpoint Therapeutics, BDO, and Genentech outside the submitted work. Dr. Farma has no disclosures other than the NCCN panel. The study was supported by Harvard Catalyst and the Harvard University Clinical and Translational Science Center and by Harvard University and its affiliated academic health care centers and partially supported by the Melvin Markey Discovery Fund at Cleveland Clinic Foundation.

CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.

For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.

When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.

There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.

Researchers from the Alliance for Clinical Trials in Oncology explained how a multifaceted approach resulted in a 75% relative improvement in trial enrollment from 2014 to 2022, a period that included a pandemic-induced hiatus in clinical trials in general.

Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.

During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.

Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.

“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.

The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
 

Program to increase underrepresented patient accrual

The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.

“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.

“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
 

What works?

The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”

“I’m going to violate the rules of your question,” Dr. Paskett replied.

“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.

She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.

Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:

• Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
• Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
• Translation of informational materials for patients.
• Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
• Real-time monitoring of accrual demographics by the Alliance and at the trial site.
• Closing protocol enrollment to majority populations.
• Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.

The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.

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

CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.

For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.

When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.

There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.

Researchers from the Alliance for Clinical Trials in Oncology explained how a multifaceted approach resulted in a 75% relative improvement in trial enrollment from 2014 to 2022, a period that included a pandemic-induced hiatus in clinical trials in general.

Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.

During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.

Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.

“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.

The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
 

Program to increase underrepresented patient accrual

The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.

“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.

“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
 

What works?

The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”

“I’m going to violate the rules of your question,” Dr. Paskett replied.

“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.

She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.

Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:

• Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
• Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
• Translation of informational materials for patients.
• Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
• Real-time monitoring of accrual demographics by the Alliance and at the trial site.
• Closing protocol enrollment to majority populations.
• Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.

The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.

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

CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.

For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.

When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.

There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.

Researchers from the Alliance for Clinical Trials in Oncology explained how a multifaceted approach resulted in a 75% relative improvement in trial enrollment from 2014 to 2022, a period that included a pandemic-induced hiatus in clinical trials in general.

Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.

During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.

Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.

“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.

The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
 

Program to increase underrepresented patient accrual

The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.

“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.

“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
 

What works?

The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”

“I’m going to violate the rules of your question,” Dr. Paskett replied.

“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.

She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.

Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:

• Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
• Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
• Translation of informational materials for patients.
• Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
• Real-time monitoring of accrual demographics by the Alliance and at the trial site.
• Closing protocol enrollment to majority populations.
• Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.

The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.

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

In this video, Dr. David Ramsay of Digestive Health Specialists in Winston Salem, N.C., discusses the different career paths available to fellows and early-career physicians, and why he chose to become a private practice gastroenterologist. Dr. Ramsay shares his insights into different private practice models and what physicians should consider when beginning their careers, as well as what questions to ask when trying to determine if an organization will be a good fit for their future career plans. He has no financial conflicts relative to the topics in this video.

Vidyard Video

In this video, Dr. David Ramsay of Digestive Health Specialists in Winston Salem, N.C., discusses the different career paths available to fellows and early-career physicians, and why he chose to become a private practice gastroenterologist. Dr. Ramsay shares his insights into different private practice models and what physicians should consider when beginning their careers, as well as what questions to ask when trying to determine if an organization will be a good fit for their future career plans. He has no financial conflicts relative to the topics in this video.

Vidyard Video

In this video, Dr. David Ramsay of Digestive Health Specialists in Winston Salem, N.C., discusses the different career paths available to fellows and early-career physicians, and why he chose to become a private practice gastroenterologist. Dr. Ramsay shares his insights into different private practice models and what physicians should consider when beginning their careers, as well as what questions to ask when trying to determine if an organization will be a good fit for their future career plans. He has no financial conflicts relative to the topics in this video.

Vidyard Video

CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.

Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.

A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.

In the randomized controlled RESTORE study, use of the cell phone–based CBSM app was associated with significantly greater reduction in symptoms of anxiety and depression compared with a digital health education control app.

In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).

However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.

The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.

“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.

“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
 

Impressive and elegant

“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.

“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.

CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.

To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.

Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.

They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
 

High-quality control

Ms. Ramiller said that the control app set “a high bar.”

“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.

A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.

The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).

CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)

An extension study of the durability of the effects at 3 and 6 months is underway.

The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.

“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”

The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
 

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

CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.

Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.

A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.

In the randomized controlled RESTORE study, use of the cell phone–based CBSM app was associated with significantly greater reduction in symptoms of anxiety and depression compared with a digital health education control app.

In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).

However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.

The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.

“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.

“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
 

Impressive and elegant

“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.

“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.

CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.

To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.

Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.

They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
 

High-quality control

Ms. Ramiller said that the control app set “a high bar.”

“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.

A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.

The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).

CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)

An extension study of the durability of the effects at 3 and 6 months is underway.

The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.

“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”

The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
 

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

CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.

Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.

A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.

In the randomized controlled RESTORE study, use of the cell phone–based CBSM app was associated with significantly greater reduction in symptoms of anxiety and depression compared with a digital health education control app.

In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).

However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.

The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.

“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.

“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
 

Impressive and elegant

“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.

“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.

CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.

To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.

Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.

They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
 

High-quality control

Ms. Ramiller said that the control app set “a high bar.”

“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.

A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.

The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).

CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)

An extension study of the durability of the effects at 3 and 6 months is underway.

The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.

“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”

The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
 

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

The Food and Drug Administration has approved the oral poly (ADP-ribose) polymerase inhibitor talazoparib (Talzenna, Pfizer) plus enzalutamide (Xtandi) to treat homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer.

Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.

The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).

Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.

Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.

“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”

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

The Food and Drug Administration has approved the oral poly (ADP-ribose) polymerase inhibitor talazoparib (Talzenna, Pfizer) plus enzalutamide (Xtandi) to treat homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer.

Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.

The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).

Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.

Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.

“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”

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

The Food and Drug Administration has approved the oral poly (ADP-ribose) polymerase inhibitor talazoparib (Talzenna, Pfizer) plus enzalutamide (Xtandi) to treat homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer.

Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.

The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).

Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.

Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.

“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”

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

TOPLINE:

A family history of breast cancer does not necessarily mean that women who have the disease are more likely to die from it.

METHODOLOGY:

• Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
• Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.

TAKEAWAYS:

• After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
• The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
• However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).

IN PRACTICE:

Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.

STUDY DETAILS:

The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.

LIMITATIONS:

• The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
• Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.

DISCLOSURES:

• The work was funded by the Swedish Cancer Society and others.
• The investigators report no relevant financial relationships.

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

TOPLINE:

A family history of breast cancer does not necessarily mean that women who have the disease are more likely to die from it.

METHODOLOGY:

• Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
• Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.

TAKEAWAYS:

• After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
• The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
• However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).

IN PRACTICE:

Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.

STUDY DETAILS:

The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.

LIMITATIONS:

• The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
• Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.

DISCLOSURES:

• The work was funded by the Swedish Cancer Society and others.
• The investigators report no relevant financial relationships.

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

TOPLINE:

A family history of breast cancer does not necessarily mean that women who have the disease are more likely to die from it.

METHODOLOGY:

• Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
• Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.

TAKEAWAYS:

• After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
• The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
• However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).

IN PRACTICE:

Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.

STUDY DETAILS:

The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.

LIMITATIONS:

• The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
• Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.

DISCLOSURES:

• The work was funded by the Swedish Cancer Society and others.
• The investigators report no relevant financial relationships.

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

CHICAGO – Trastuzumab deruxtecan (T-DXd) (Enhertu) already has proven efficacy against HER2-expressing metastatic breast, gastroesophageal, and lung cancers.

Now, preliminary data from an ongoing study indicate that T-DXd, which combines an antibody targeted to HER2 with a toxic payload, could be an effective therapy for a broader range of advanced solid tumors that express HER2, including malignancies of the cervix, endometrium, ovaries, bladder, and other sites.

The findings come from the ongoing DESTINY-PanTumor02 trial. Among 267 patients with solid tumors at various organ sites, the investigator-assessed objective response rate among all patients was 37.1%, and ranged from as high as 57.5% for patients with endometrial cancers to as low as 4% for patients with pancreatic cancer, reported Funda Meric-Bernstam, MD, from the University of Texas MD Anderson Cancer Center, Houston.

For patients with tumors that had HER2 immunohistochemistry (IHC) scores of 3+, the highest level of HER2 expression, the overall response rate was 61.3%..

The responses were also durable, with a median duration of 11.8 months among all patients and 22.1 months among patients with IHC 3+ scores.

“Our data to date showed that T-DXd had clinically meaningful activity across a variety of tumor types,” she said in a briefing held prior to her presentation of the data at the annual meeting of the American Society of Clinical Oncology.

“HER2 expression has been around a long time. We think about this all the time in breast cancer and drugs are approved there, but HER2 is expressed in other tumors as well, and that really represents an unmet need, because we have limited options in this situation” commented ASCO expert Bradley Alexander McGregor, MD, from the Dana-Farber Cancer Institute, Boston, an invited discussant at the briefing.

“Aside from pancreatic cancer we saw really, really encouraging results with no new safety signals, so while early I think this really exciting and represents a shift in how we think about cancer care,” he added.

After the presentation, invited discussant Kohei Shitara, MD, of National Cancer Center Hospital East, Kashiwa, Japan, said that he agrees with authors that T-DXd is a potential new treatment option for patients with HER2-expressing solid tumors, and that the evidence suggests the potential for further tumor-agnostic development of the agent.

He cautioned, however, that there is a lack of concordance between local and central assessment of HER2 IHC, and that quality assurance will be required to ensure that the HER2 status of solid tumors is accurately characterized.

At a press briefing, Dr. Meric-Bernstam was asked how she envisioned using T-DXd in therapy for various HER2-expressing tumors.

“I think the activity we’ve seen is quite compelling, and one hopes that eventually this will be a drug that’s accessible for patients that are HER2-expressing across tumor types. Clearly, the activity is very compelling in some of the diseases to think about doing studies for earlier lines,” she said.

“The data indicate that there is tumor-agnostic activity across the board,” she said, but noted that tumors with epithelial components such as ovarian and breast cancers appear to have the highest responses to T-DXd therapy.

Briefing moderator Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, asked Dr. McGregor whether, in the light of this new data, oncologists should test more patients for HER2 expression.

“We have some cancers where we know HER2 expression is there. I think the good thing about HER2 testing is that it’s an IHC test, so this is something that can be easily done in local pathology [labs],” he said. As more evidence mounts of potential benefit of T-DXd in HER2 expressing tumors, clinicians will need to consider more routine HER2 testing.
 

A rendezvous with DESTINY

The DESTINY-PanTumor02 trial is a phase 2, open-label, multicenter study looking at T-DXd in patients with advanced solid tumors who are not eligible for therapy with curative intent.

All patients had disease progression after at least two prior lines of therapy, and had tumors with HER2 expression of IHC 3+ or 2+ either by local or central testing. Patients were allowed to have previously received HER2-targeting therapy. Patients also had to have good performance status (Eastern Cooperative Oncology Group/World Health Organization performance status 0 or 1).

The investigators planned to enroll 40 patients in each cohort, including patients with cervical, endometrial, ovarian, biliary tract, pancreatic, or bladder cancers, as well those with other tumors expressing HER2 who were not included in the other cohorts.

Under the protocol, cohorts in which none of the first 15 patients had objective responses would be closed, as happened with the pancreatic cancer cohort.

At a median follow-up of 9.7 months, an objective response was seen in 99 patients out of the 267 in the entire study population (ORR, 37.1%). This ORR consisted of 15 complete responses and 84 partial responses. An additional 123 patients had stable disease.

An analysis of ORR by HER2 expression showed that IHC 3+ expressing tumors had rates ranging from 84.6% in endometrial cancers, 75% in cervical cancer, 63.6% in ovarian cancers, and 56.3% in bladder cancers, down to zero in IHC 3+ expressing pancreatic cancer. 

The T-DXd safety profile was consistent with that seen in other clinical trials, with most common adverse events being nausea, fatigue, neutropenia, anemia, diarrhea, and thrombocytopenia. There were 20 cases of interstitial lung disease, one of which was fatal.

The trial is ongoing, and investigators plan to report overall survival and progression-free survival results with additional follow-up.

DESTINY-PanTumor02 is funded by Daiichi Sankyo. Dr. Meric-Bernstam disclosed a consulting/advisory role with multiple pharmaceutical companies, research funding to her institution from Daiichi Sankyo and others, and travel expenses from ESMO and EORTC. Dr. McGregor disclosed a consulting/advisory role and institutional research funding with multiple companies, not including the study’s funder. Dr. Gralow disclosed a consulting or advisory role with Genentech and Roche.

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

CHICAGO – Trastuzumab deruxtecan (T-DXd) (Enhertu) already has proven efficacy against HER2-expressing metastatic breast, gastroesophageal, and lung cancers.

Now, preliminary data from an ongoing study indicate that T-DXd, which combines an antibody targeted to HER2 with a toxic payload, could be an effective therapy for a broader range of advanced solid tumors that express HER2, including malignancies of the cervix, endometrium, ovaries, bladder, and other sites.

The findings come from the ongoing DESTINY-PanTumor02 trial. Among 267 patients with solid tumors at various organ sites, the investigator-assessed objective response rate among all patients was 37.1%, and ranged from as high as 57.5% for patients with endometrial cancers to as low as 4% for patients with pancreatic cancer, reported Funda Meric-Bernstam, MD, from the University of Texas MD Anderson Cancer Center, Houston.

For patients with tumors that had HER2 immunohistochemistry (IHC) scores of 3+, the highest level of HER2 expression, the overall response rate was 61.3%..

The responses were also durable, with a median duration of 11.8 months among all patients and 22.1 months among patients with IHC 3+ scores.

“Our data to date showed that T-DXd had clinically meaningful activity across a variety of tumor types,” she said in a briefing held prior to her presentation of the data at the annual meeting of the American Society of Clinical Oncology.

“HER2 expression has been around a long time. We think about this all the time in breast cancer and drugs are approved there, but HER2 is expressed in other tumors as well, and that really represents an unmet need, because we have limited options in this situation” commented ASCO expert Bradley Alexander McGregor, MD, from the Dana-Farber Cancer Institute, Boston, an invited discussant at the briefing.

“Aside from pancreatic cancer we saw really, really encouraging results with no new safety signals, so while early I think this really exciting and represents a shift in how we think about cancer care,” he added.

After the presentation, invited discussant Kohei Shitara, MD, of National Cancer Center Hospital East, Kashiwa, Japan, said that he agrees with authors that T-DXd is a potential new treatment option for patients with HER2-expressing solid tumors, and that the evidence suggests the potential for further tumor-agnostic development of the agent.

He cautioned, however, that there is a lack of concordance between local and central assessment of HER2 IHC, and that quality assurance will be required to ensure that the HER2 status of solid tumors is accurately characterized.

At a press briefing, Dr. Meric-Bernstam was asked how she envisioned using T-DXd in therapy for various HER2-expressing tumors.

“I think the activity we’ve seen is quite compelling, and one hopes that eventually this will be a drug that’s accessible for patients that are HER2-expressing across tumor types. Clearly, the activity is very compelling in some of the diseases to think about doing studies for earlier lines,” she said.

“The data indicate that there is tumor-agnostic activity across the board,” she said, but noted that tumors with epithelial components such as ovarian and breast cancers appear to have the highest responses to T-DXd therapy.

Briefing moderator Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, asked Dr. McGregor whether, in the light of this new data, oncologists should test more patients for HER2 expression.

“We have some cancers where we know HER2 expression is there. I think the good thing about HER2 testing is that it’s an IHC test, so this is something that can be easily done in local pathology [labs],” he said. As more evidence mounts of potential benefit of T-DXd in HER2 expressing tumors, clinicians will need to consider more routine HER2 testing.
 

A rendezvous with DESTINY

The DESTINY-PanTumor02 trial is a phase 2, open-label, multicenter study looking at T-DXd in patients with advanced solid tumors who are not eligible for therapy with curative intent.

All patients had disease progression after at least two prior lines of therapy, and had tumors with HER2 expression of IHC 3+ or 2+ either by local or central testing. Patients were allowed to have previously received HER2-targeting therapy. Patients also had to have good performance status (Eastern Cooperative Oncology Group/World Health Organization performance status 0 or 1).

The investigators planned to enroll 40 patients in each cohort, including patients with cervical, endometrial, ovarian, biliary tract, pancreatic, or bladder cancers, as well those with other tumors expressing HER2 who were not included in the other cohorts.

Under the protocol, cohorts in which none of the first 15 patients had objective responses would be closed, as happened with the pancreatic cancer cohort.

At a median follow-up of 9.7 months, an objective response was seen in 99 patients out of the 267 in the entire study population (ORR, 37.1%). This ORR consisted of 15 complete responses and 84 partial responses. An additional 123 patients had stable disease.

An analysis of ORR by HER2 expression showed that IHC 3+ expressing tumors had rates ranging from 84.6% in endometrial cancers, 75% in cervical cancer, 63.6% in ovarian cancers, and 56.3% in bladder cancers, down to zero in IHC 3+ expressing pancreatic cancer. 

The T-DXd safety profile was consistent with that seen in other clinical trials, with most common adverse events being nausea, fatigue, neutropenia, anemia, diarrhea, and thrombocytopenia. There were 20 cases of interstitial lung disease, one of which was fatal.

The trial is ongoing, and investigators plan to report overall survival and progression-free survival results with additional follow-up.

DESTINY-PanTumor02 is funded by Daiichi Sankyo. Dr. Meric-Bernstam disclosed a consulting/advisory role with multiple pharmaceutical companies, research funding to her institution from Daiichi Sankyo and others, and travel expenses from ESMO and EORTC. Dr. McGregor disclosed a consulting/advisory role and institutional research funding with multiple companies, not including the study’s funder. Dr. Gralow disclosed a consulting or advisory role with Genentech and Roche.

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

CHICAGO – Trastuzumab deruxtecan (T-DXd) (Enhertu) already has proven efficacy against HER2-expressing metastatic breast, gastroesophageal, and lung cancers.

Now, preliminary data from an ongoing study indicate that T-DXd, which combines an antibody targeted to HER2 with a toxic payload, could be an effective therapy for a broader range of advanced solid tumors that express HER2, including malignancies of the cervix, endometrium, ovaries, bladder, and other sites.

The findings come from the ongoing DESTINY-PanTumor02 trial. Among 267 patients with solid tumors at various organ sites, the investigator-assessed objective response rate among all patients was 37.1%, and ranged from as high as 57.5% for patients with endometrial cancers to as low as 4% for patients with pancreatic cancer, reported Funda Meric-Bernstam, MD, from the University of Texas MD Anderson Cancer Center, Houston.

For patients with tumors that had HER2 immunohistochemistry (IHC) scores of 3+, the highest level of HER2 expression, the overall response rate was 61.3%..

The responses were also durable, with a median duration of 11.8 months among all patients and 22.1 months among patients with IHC 3+ scores.

“Our data to date showed that T-DXd had clinically meaningful activity across a variety of tumor types,” she said in a briefing held prior to her presentation of the data at the annual meeting of the American Society of Clinical Oncology.

“HER2 expression has been around a long time. We think about this all the time in breast cancer and drugs are approved there, but HER2 is expressed in other tumors as well, and that really represents an unmet need, because we have limited options in this situation” commented ASCO expert Bradley Alexander McGregor, MD, from the Dana-Farber Cancer Institute, Boston, an invited discussant at the briefing.

“Aside from pancreatic cancer we saw really, really encouraging results with no new safety signals, so while early I think this really exciting and represents a shift in how we think about cancer care,” he added.

After the presentation, invited discussant Kohei Shitara, MD, of National Cancer Center Hospital East, Kashiwa, Japan, said that he agrees with authors that T-DXd is a potential new treatment option for patients with HER2-expressing solid tumors, and that the evidence suggests the potential for further tumor-agnostic development of the agent.

He cautioned, however, that there is a lack of concordance between local and central assessment of HER2 IHC, and that quality assurance will be required to ensure that the HER2 status of solid tumors is accurately characterized.

At a press briefing, Dr. Meric-Bernstam was asked how she envisioned using T-DXd in therapy for various HER2-expressing tumors.

“I think the activity we’ve seen is quite compelling, and one hopes that eventually this will be a drug that’s accessible for patients that are HER2-expressing across tumor types. Clearly, the activity is very compelling in some of the diseases to think about doing studies for earlier lines,” she said.

“The data indicate that there is tumor-agnostic activity across the board,” she said, but noted that tumors with epithelial components such as ovarian and breast cancers appear to have the highest responses to T-DXd therapy.

Briefing moderator Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, asked Dr. McGregor whether, in the light of this new data, oncologists should test more patients for HER2 expression.

“We have some cancers where we know HER2 expression is there. I think the good thing about HER2 testing is that it’s an IHC test, so this is something that can be easily done in local pathology [labs],” he said. As more evidence mounts of potential benefit of T-DXd in HER2 expressing tumors, clinicians will need to consider more routine HER2 testing.
 

A rendezvous with DESTINY

The DESTINY-PanTumor02 trial is a phase 2, open-label, multicenter study looking at T-DXd in patients with advanced solid tumors who are not eligible for therapy with curative intent.

All patients had disease progression after at least two prior lines of therapy, and had tumors with HER2 expression of IHC 3+ or 2+ either by local or central testing. Patients were allowed to have previously received HER2-targeting therapy. Patients also had to have good performance status (Eastern Cooperative Oncology Group/World Health Organization performance status 0 or 1).

The investigators planned to enroll 40 patients in each cohort, including patients with cervical, endometrial, ovarian, biliary tract, pancreatic, or bladder cancers, as well those with other tumors expressing HER2 who were not included in the other cohorts.

Under the protocol, cohorts in which none of the first 15 patients had objective responses would be closed, as happened with the pancreatic cancer cohort.

At a median follow-up of 9.7 months, an objective response was seen in 99 patients out of the 267 in the entire study population (ORR, 37.1%). This ORR consisted of 15 complete responses and 84 partial responses. An additional 123 patients had stable disease.

An analysis of ORR by HER2 expression showed that IHC 3+ expressing tumors had rates ranging from 84.6% in endometrial cancers, 75% in cervical cancer, 63.6% in ovarian cancers, and 56.3% in bladder cancers, down to zero in IHC 3+ expressing pancreatic cancer. 

The T-DXd safety profile was consistent with that seen in other clinical trials, with most common adverse events being nausea, fatigue, neutropenia, anemia, diarrhea, and thrombocytopenia. There were 20 cases of interstitial lung disease, one of which was fatal.

The trial is ongoing, and investigators plan to report overall survival and progression-free survival results with additional follow-up.

DESTINY-PanTumor02 is funded by Daiichi Sankyo. Dr. Meric-Bernstam disclosed a consulting/advisory role with multiple pharmaceutical companies, research funding to her institution from Daiichi Sankyo and others, and travel expenses from ESMO and EORTC. Dr. McGregor disclosed a consulting/advisory role and institutional research funding with multiple companies, not including the study’s funder. Dr. Gralow disclosed a consulting or advisory role with Genentech and Roche.

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