Roxanne Nelson, RN, BSN

Adjuvant therapy for patients with high-risk resected melanomas is now a standard of care, but the durability of the benefit gained from this treatment is still unclear.

New data show that the benefit is maintained over the longer term.

At 5 years, just over half of patients (52%) with advanced melanoma who had received a year of adjuvant therapy with two targeted agents were still alive and remained relapse free, compared with 36% of patients who received placebo.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) conferred a durable long-term, relapse-free survival benefit for patients with resected stage III melanoma with BRAF V600E or V600K mutations, the investigators concluded.

These data come from the COMBI-AD phase 3 trial and were published online in the New England Journal of Medicine.

“The treatment duration of this adjuvant therapy was 12 months; however, we do not know whether this is the optimal treatment duration,” said lead author Reinhard Dummer, MD, vice chairman, department of dermatology, University of Zürich Hospital. “Early biomarker results suggest that, in a subgroup, longer treatment durations might be necessary. In other patients, a shorter treatment could be sufficient.”

Richard Carvajal, MD, director of the Melanoma Service at New York–Presbyterian Hospital and Columbia University Medical Center, also in New York, said the new data “address prior concerns that any benefit achieved with targeted therapy in the adjuvant setting may be limited in duration.”

“Indeed, with active therapy, over 50% of patients are alive without relapse and 65% of patients are alive without the development of distant metastasis,” he said. “Although overall survival data remain immature, numerical improvement in survival is also reported.”

In an interview, Dr. Carvajal said that the plateaus observed with relapse and distant metastasis-free survival suggest that true disease cures are being achieved with treatment. “Based upon these results, the discussion of adjuvant therapeutic options should include a 12-month course of adjuvant dabrafenib and trametinib, as well as the option of adjuvant anti-PD-1 [programmed death–1] therapy.”

As for how the MEK-BRAF inhibitor combination compares with immunotherapy in this setting, he pointed out that, since there has been no head-to-head comparison of adjuvant targeted therapy and adjuvant nivolumab (Opdivo) or pembrolizumab (Keytruda), it is not possible to conclusively state that one regimen is more effective than another.

“For patients with resected BRAF-mutant melanoma at high risk of disease recurrence, we now have data demonstrating the clinical benefit for a course of adjuvant dabrafenib and trametinib, adjuvant nivolumab and adjuvant pembrolizumab,” said Dr. Carvajal.

“Although the efficacy of adjuvant ipilimumab [Yervoy] as well as adjuvant interferon have also been previously demonstrated, these agents are now appropriate for consideration in extremely rare clinical circumstances given the clinical efficacy and improved toxicity profile of single agent anti-PD-1 therapy.”

“The selection of the most appropriate adjuvant therapy should take into account the preferences of individual patients in terms of toxicity profile and drug administration considerations,” he added.


 

Study details

The COMBI-AD was a randomized, double-blind, placebo-controlled, phase 3 study conducted in 870 patients with high-risk, stage III, BRAF-V600E/K–mutant melanoma who were treatment naive. Participating patients had undergone surgical resection and had been disease free for ≤12 weeks.

Interim results from this study, reported in 2017, showed 1 year of oral adjuvant therapy with dabrafenib and trametinib provided a 53% lower risk for 3-year recurrence, compared with placebo.

Now, the investigators reported on the 5-year results for relapse-free survival and survival without distant metastasis. They noted that they were unable to analyze overall survival since the required number of events had not been reached.

Patients had been randomly assigned to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Patients were followed for 60 months (5 years) for dabrafenib plus trametinib and 58 months for placebo.

At 5 years, the median relapse-free survival was not reached for patients who received the combination therapy group versus 16.6 months in the placebo group (hazard ratio for relapse or death, 0.51).

The percentage of patients who were alive without distant metastasis at 5 years was 65% in the dabrafenib plus trametinib group and 54% in the placebo arm (HR for distant metastasis or death, 0.55).

The hazard ratio for relapse-free survival favored dabrafenib plus trametinib across all patient subgroups that were evaluated in the study, and survival without distant metastasis showed a similar benefit for the combination regardless of disease stage.

Subsequent therapy was needed in 40% of patients who received dabrafenib plus trametinib and by 54% of those in the placebo group, with the most common treatments being immunotherapy in the combination-therapy group [26%] and small molecule–targeted therapy in the placebo group (35%).
 

A viable option

Dr. Dummer noted that, when this clinical trial was designed, all patients had to undergo aggressive surgery that involved lymph node dissection. “Nowadays, based on the lack of improvement on progression-free survival and overall survival, the surgical procedures are less aggressive and today we do not recommend aggressive lymph node dissection in patients that qualify for adjuvant therapy. In patients that do not have the BRAF mutation, there is the possibility of giving immunotherapy.”

He added that there is an urgent need for biomarkers that can identify early progression during adjuvant therapy. “Potentially, these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy,” Dr. Dummer said.

The study was funded by GlaxoSmithKline and Novartis. Dr. Dummer has declared multiple relationships with industry.

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

Adjuvant therapy for patients with high-risk resected melanomas is now a standard of care, but the durability of the benefit gained from this treatment is still unclear.

New data show that the benefit is maintained over the longer term.

At 5 years, just over half of patients (52%) with advanced melanoma who had received a year of adjuvant therapy with two targeted agents were still alive and remained relapse free, compared with 36% of patients who received placebo.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) conferred a durable long-term, relapse-free survival benefit for patients with resected stage III melanoma with BRAF V600E or V600K mutations, the investigators concluded.

These data come from the COMBI-AD phase 3 trial and were published online in the New England Journal of Medicine.

“The treatment duration of this adjuvant therapy was 12 months; however, we do not know whether this is the optimal treatment duration,” said lead author Reinhard Dummer, MD, vice chairman, department of dermatology, University of Zürich Hospital. “Early biomarker results suggest that, in a subgroup, longer treatment durations might be necessary. In other patients, a shorter treatment could be sufficient.”

Richard Carvajal, MD, director of the Melanoma Service at New York–Presbyterian Hospital and Columbia University Medical Center, also in New York, said the new data “address prior concerns that any benefit achieved with targeted therapy in the adjuvant setting may be limited in duration.”

“Indeed, with active therapy, over 50% of patients are alive without relapse and 65% of patients are alive without the development of distant metastasis,” he said. “Although overall survival data remain immature, numerical improvement in survival is also reported.”

In an interview, Dr. Carvajal said that the plateaus observed with relapse and distant metastasis-free survival suggest that true disease cures are being achieved with treatment. “Based upon these results, the discussion of adjuvant therapeutic options should include a 12-month course of adjuvant dabrafenib and trametinib, as well as the option of adjuvant anti-PD-1 [programmed death–1] therapy.”

As for how the MEK-BRAF inhibitor combination compares with immunotherapy in this setting, he pointed out that, since there has been no head-to-head comparison of adjuvant targeted therapy and adjuvant nivolumab (Opdivo) or pembrolizumab (Keytruda), it is not possible to conclusively state that one regimen is more effective than another.

“For patients with resected BRAF-mutant melanoma at high risk of disease recurrence, we now have data demonstrating the clinical benefit for a course of adjuvant dabrafenib and trametinib, adjuvant nivolumab and adjuvant pembrolizumab,” said Dr. Carvajal.

“Although the efficacy of adjuvant ipilimumab [Yervoy] as well as adjuvant interferon have also been previously demonstrated, these agents are now appropriate for consideration in extremely rare clinical circumstances given the clinical efficacy and improved toxicity profile of single agent anti-PD-1 therapy.”

“The selection of the most appropriate adjuvant therapy should take into account the preferences of individual patients in terms of toxicity profile and drug administration considerations,” he added.


 

Study details

The COMBI-AD was a randomized, double-blind, placebo-controlled, phase 3 study conducted in 870 patients with high-risk, stage III, BRAF-V600E/K–mutant melanoma who were treatment naive. Participating patients had undergone surgical resection and had been disease free for ≤12 weeks.

Interim results from this study, reported in 2017, showed 1 year of oral adjuvant therapy with dabrafenib and trametinib provided a 53% lower risk for 3-year recurrence, compared with placebo.

Now, the investigators reported on the 5-year results for relapse-free survival and survival without distant metastasis. They noted that they were unable to analyze overall survival since the required number of events had not been reached.

Patients had been randomly assigned to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Patients were followed for 60 months (5 years) for dabrafenib plus trametinib and 58 months for placebo.

At 5 years, the median relapse-free survival was not reached for patients who received the combination therapy group versus 16.6 months in the placebo group (hazard ratio for relapse or death, 0.51).

The percentage of patients who were alive without distant metastasis at 5 years was 65% in the dabrafenib plus trametinib group and 54% in the placebo arm (HR for distant metastasis or death, 0.55).

The hazard ratio for relapse-free survival favored dabrafenib plus trametinib across all patient subgroups that were evaluated in the study, and survival without distant metastasis showed a similar benefit for the combination regardless of disease stage.

Subsequent therapy was needed in 40% of patients who received dabrafenib plus trametinib and by 54% of those in the placebo group, with the most common treatments being immunotherapy in the combination-therapy group [26%] and small molecule–targeted therapy in the placebo group (35%).
 

A viable option

Dr. Dummer noted that, when this clinical trial was designed, all patients had to undergo aggressive surgery that involved lymph node dissection. “Nowadays, based on the lack of improvement on progression-free survival and overall survival, the surgical procedures are less aggressive and today we do not recommend aggressive lymph node dissection in patients that qualify for adjuvant therapy. In patients that do not have the BRAF mutation, there is the possibility of giving immunotherapy.”

He added that there is an urgent need for biomarkers that can identify early progression during adjuvant therapy. “Potentially, these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy,” Dr. Dummer said.

The study was funded by GlaxoSmithKline and Novartis. Dr. Dummer has declared multiple relationships with industry.

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

Adjuvant therapy for patients with high-risk resected melanomas is now a standard of care, but the durability of the benefit gained from this treatment is still unclear.

New data show that the benefit is maintained over the longer term.

At 5 years, just over half of patients (52%) with advanced melanoma who had received a year of adjuvant therapy with two targeted agents were still alive and remained relapse free, compared with 36% of patients who received placebo.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) conferred a durable long-term, relapse-free survival benefit for patients with resected stage III melanoma with BRAF V600E or V600K mutations, the investigators concluded.

These data come from the COMBI-AD phase 3 trial and were published online in the New England Journal of Medicine.

“The treatment duration of this adjuvant therapy was 12 months; however, we do not know whether this is the optimal treatment duration,” said lead author Reinhard Dummer, MD, vice chairman, department of dermatology, University of Zürich Hospital. “Early biomarker results suggest that, in a subgroup, longer treatment durations might be necessary. In other patients, a shorter treatment could be sufficient.”

Richard Carvajal, MD, director of the Melanoma Service at New York–Presbyterian Hospital and Columbia University Medical Center, also in New York, said the new data “address prior concerns that any benefit achieved with targeted therapy in the adjuvant setting may be limited in duration.”

“Indeed, with active therapy, over 50% of patients are alive without relapse and 65% of patients are alive without the development of distant metastasis,” he said. “Although overall survival data remain immature, numerical improvement in survival is also reported.”

In an interview, Dr. Carvajal said that the plateaus observed with relapse and distant metastasis-free survival suggest that true disease cures are being achieved with treatment. “Based upon these results, the discussion of adjuvant therapeutic options should include a 12-month course of adjuvant dabrafenib and trametinib, as well as the option of adjuvant anti-PD-1 [programmed death–1] therapy.”

As for how the MEK-BRAF inhibitor combination compares with immunotherapy in this setting, he pointed out that, since there has been no head-to-head comparison of adjuvant targeted therapy and adjuvant nivolumab (Opdivo) or pembrolizumab (Keytruda), it is not possible to conclusively state that one regimen is more effective than another.

“For patients with resected BRAF-mutant melanoma at high risk of disease recurrence, we now have data demonstrating the clinical benefit for a course of adjuvant dabrafenib and trametinib, adjuvant nivolumab and adjuvant pembrolizumab,” said Dr. Carvajal.

“Although the efficacy of adjuvant ipilimumab [Yervoy] as well as adjuvant interferon have also been previously demonstrated, these agents are now appropriate for consideration in extremely rare clinical circumstances given the clinical efficacy and improved toxicity profile of single agent anti-PD-1 therapy.”

“The selection of the most appropriate adjuvant therapy should take into account the preferences of individual patients in terms of toxicity profile and drug administration considerations,” he added.


 

Study details

The COMBI-AD was a randomized, double-blind, placebo-controlled, phase 3 study conducted in 870 patients with high-risk, stage III, BRAF-V600E/K–mutant melanoma who were treatment naive. Participating patients had undergone surgical resection and had been disease free for ≤12 weeks.

Interim results from this study, reported in 2017, showed 1 year of oral adjuvant therapy with dabrafenib and trametinib provided a 53% lower risk for 3-year recurrence, compared with placebo.

Now, the investigators reported on the 5-year results for relapse-free survival and survival without distant metastasis. They noted that they were unable to analyze overall survival since the required number of events had not been reached.

Patients had been randomly assigned to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Patients were followed for 60 months (5 years) for dabrafenib plus trametinib and 58 months for placebo.

At 5 years, the median relapse-free survival was not reached for patients who received the combination therapy group versus 16.6 months in the placebo group (hazard ratio for relapse or death, 0.51).

The percentage of patients who were alive without distant metastasis at 5 years was 65% in the dabrafenib plus trametinib group and 54% in the placebo arm (HR for distant metastasis or death, 0.55).

The hazard ratio for relapse-free survival favored dabrafenib plus trametinib across all patient subgroups that were evaluated in the study, and survival without distant metastasis showed a similar benefit for the combination regardless of disease stage.

Subsequent therapy was needed in 40% of patients who received dabrafenib plus trametinib and by 54% of those in the placebo group, with the most common treatments being immunotherapy in the combination-therapy group [26%] and small molecule–targeted therapy in the placebo group (35%).
 

A viable option

Dr. Dummer noted that, when this clinical trial was designed, all patients had to undergo aggressive surgery that involved lymph node dissection. “Nowadays, based on the lack of improvement on progression-free survival and overall survival, the surgical procedures are less aggressive and today we do not recommend aggressive lymph node dissection in patients that qualify for adjuvant therapy. In patients that do not have the BRAF mutation, there is the possibility of giving immunotherapy.”

He added that there is an urgent need for biomarkers that can identify early progression during adjuvant therapy. “Potentially, these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy,” Dr. Dummer said.

The study was funded by GlaxoSmithKline and Novartis. Dr. Dummer has declared multiple relationships with industry.

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

The Food and Drug Administration has approved an oral form of azacitidine (Onureg) for use as maintenance therapy for patients with acute myeloid leukemia (AML) who have achieved a first complete remission.

The approval extends to patients who have achieved complete remission with incomplete blood count recovery following intensive induction chemotherapy and who are unable to complete intensive curative therapy.

The approval was based on data from the QUAZAR AML-001 trial, which showed that oral azacitidine significantly improved overall survival when compared with placebo.

“It’s not too hard to get these patients into remission,” Harry P. Erba, MD, PhD, director of the Leukemia Program at the Duke Cancer Institute, Durham, N.C., said in an interview last year when these results were first presented at the 2019 annual meeting of the American Society of Hematology. “The problem comes in keeping them in remission.”

Despite various attempts, there has been no success over the past 30 years in defining maintenance treatment for these patients, Andrew H. Wei, MBBS, PhD, from the Alfred Hospital in Melbourne, Australia, said.

“Oral azacitidine represents a new therapeutic standard for patients with AML in remission,” he said.

Azacitidine is a hypomethylating agent that incorporates into DNA and RNA. It has long been used as an injectable therapy for the treatment of myelodysplastic syndromes.

The approval of the new oral formulation for the new indication of AML “is the culmination of over a decade of research and 13 preclinical and clinical trials,” said Giovanni Caforio, M.D., chairman and chief executive officer of Bristol-Myers Squibb, in a statement.

QUAZAR results

The QUAZAR AML-001 trial was a phase 3, international study involving 472 patients with AML who were within achieving a first complete remission or remission with incomplete blood recovery. All patients had received intensive induction chemotherapy with or without consolidation treatment per investigator preference prior to study entry and were not candidates for hematopoietic stem cell transplant at the time of screening.

Patients were randomly assigned to receive either oral azacitidine 200 mg daily on days 1-14 of a repeat 28-day cycle (n = 278) or matching placebo (n = 274). Treatment was continued indefinitely until blast count was more than 15% or patients experienced unacceptable toxicity or underwent transplant.

At a median follow-up of more than 41.2 months, the median overall survival was significantly longer for patients who received oral azacitidine at 24.7 months versus 14.8 months for those who received placebo (hazard ratio, 0.69; P < .0009).

Relapse-free survival was also significantly prolonged to 10.2 months for patients who received oral azacitidine vs. 4.8 months for those who received placebo (HR, 0.65; P < .0001).

Serious adverse reactions occurred in 15% of patients who received azacitidine. Events that occurred in 2% of patients or more include pneumonia (8%) and febrile neutropenia (7%). There was one fatal event.

The most common adverse reactions were nausea (65% vs. 24%), vomiting (60% vs. 10%), diarrhea (50% vs. 21%), fatigue/asthenia (44% vs. 25%), constipation (39% vs. 24%), pneumonia (27% vs. 17%), abdominal pain (22% vs. 13%) arthralgia (14% vs. 10%), decreased appetite (13% vs. 6%), febrile neutropenia (12% vs. 8%), dizziness (11% vs. 9%), and pain in extremity (11% vs. 5%). Permanent discontinuation because of an adverse reaction occurred in 8% of patients.
 

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

The Food and Drug Administration has approved an oral form of azacitidine (Onureg) for use as maintenance therapy for patients with acute myeloid leukemia (AML) who have achieved a first complete remission.

The approval extends to patients who have achieved complete remission with incomplete blood count recovery following intensive induction chemotherapy and who are unable to complete intensive curative therapy.

The approval was based on data from the QUAZAR AML-001 trial, which showed that oral azacitidine significantly improved overall survival when compared with placebo.

“It’s not too hard to get these patients into remission,” Harry P. Erba, MD, PhD, director of the Leukemia Program at the Duke Cancer Institute, Durham, N.C., said in an interview last year when these results were first presented at the 2019 annual meeting of the American Society of Hematology. “The problem comes in keeping them in remission.”

Despite various attempts, there has been no success over the past 30 years in defining maintenance treatment for these patients, Andrew H. Wei, MBBS, PhD, from the Alfred Hospital in Melbourne, Australia, said.

“Oral azacitidine represents a new therapeutic standard for patients with AML in remission,” he said.

Azacitidine is a hypomethylating agent that incorporates into DNA and RNA. It has long been used as an injectable therapy for the treatment of myelodysplastic syndromes.

The approval of the new oral formulation for the new indication of AML “is the culmination of over a decade of research and 13 preclinical and clinical trials,” said Giovanni Caforio, M.D., chairman and chief executive officer of Bristol-Myers Squibb, in a statement.

QUAZAR results

The QUAZAR AML-001 trial was a phase 3, international study involving 472 patients with AML who were within achieving a first complete remission or remission with incomplete blood recovery. All patients had received intensive induction chemotherapy with or without consolidation treatment per investigator preference prior to study entry and were not candidates for hematopoietic stem cell transplant at the time of screening.

Patients were randomly assigned to receive either oral azacitidine 200 mg daily on days 1-14 of a repeat 28-day cycle (n = 278) or matching placebo (n = 274). Treatment was continued indefinitely until blast count was more than 15% or patients experienced unacceptable toxicity or underwent transplant.

At a median follow-up of more than 41.2 months, the median overall survival was significantly longer for patients who received oral azacitidine at 24.7 months versus 14.8 months for those who received placebo (hazard ratio, 0.69; P < .0009).

Relapse-free survival was also significantly prolonged to 10.2 months for patients who received oral azacitidine vs. 4.8 months for those who received placebo (HR, 0.65; P < .0001).

Serious adverse reactions occurred in 15% of patients who received azacitidine. Events that occurred in 2% of patients or more include pneumonia (8%) and febrile neutropenia (7%). There was one fatal event.

The most common adverse reactions were nausea (65% vs. 24%), vomiting (60% vs. 10%), diarrhea (50% vs. 21%), fatigue/asthenia (44% vs. 25%), constipation (39% vs. 24%), pneumonia (27% vs. 17%), abdominal pain (22% vs. 13%) arthralgia (14% vs. 10%), decreased appetite (13% vs. 6%), febrile neutropenia (12% vs. 8%), dizziness (11% vs. 9%), and pain in extremity (11% vs. 5%). Permanent discontinuation because of an adverse reaction occurred in 8% of patients.
 

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

The Food and Drug Administration has approved an oral form of azacitidine (Onureg) for use as maintenance therapy for patients with acute myeloid leukemia (AML) who have achieved a first complete remission.

The approval extends to patients who have achieved complete remission with incomplete blood count recovery following intensive induction chemotherapy and who are unable to complete intensive curative therapy.

The approval was based on data from the QUAZAR AML-001 trial, which showed that oral azacitidine significantly improved overall survival when compared with placebo.

“It’s not too hard to get these patients into remission,” Harry P. Erba, MD, PhD, director of the Leukemia Program at the Duke Cancer Institute, Durham, N.C., said in an interview last year when these results were first presented at the 2019 annual meeting of the American Society of Hematology. “The problem comes in keeping them in remission.”

Despite various attempts, there has been no success over the past 30 years in defining maintenance treatment for these patients, Andrew H. Wei, MBBS, PhD, from the Alfred Hospital in Melbourne, Australia, said.

“Oral azacitidine represents a new therapeutic standard for patients with AML in remission,” he said.

Azacitidine is a hypomethylating agent that incorporates into DNA and RNA. It has long been used as an injectable therapy for the treatment of myelodysplastic syndromes.

The approval of the new oral formulation for the new indication of AML “is the culmination of over a decade of research and 13 preclinical and clinical trials,” said Giovanni Caforio, M.D., chairman and chief executive officer of Bristol-Myers Squibb, in a statement.

QUAZAR results

The QUAZAR AML-001 trial was a phase 3, international study involving 472 patients with AML who were within achieving a first complete remission or remission with incomplete blood recovery. All patients had received intensive induction chemotherapy with or without consolidation treatment per investigator preference prior to study entry and were not candidates for hematopoietic stem cell transplant at the time of screening.

Patients were randomly assigned to receive either oral azacitidine 200 mg daily on days 1-14 of a repeat 28-day cycle (n = 278) or matching placebo (n = 274). Treatment was continued indefinitely until blast count was more than 15% or patients experienced unacceptable toxicity or underwent transplant.

At a median follow-up of more than 41.2 months, the median overall survival was significantly longer for patients who received oral azacitidine at 24.7 months versus 14.8 months for those who received placebo (hazard ratio, 0.69; P < .0009).

Relapse-free survival was also significantly prolonged to 10.2 months for patients who received oral azacitidine vs. 4.8 months for those who received placebo (HR, 0.65; P < .0001).

Serious adverse reactions occurred in 15% of patients who received azacitidine. Events that occurred in 2% of patients or more include pneumonia (8%) and febrile neutropenia (7%). There was one fatal event.

The most common adverse reactions were nausea (65% vs. 24%), vomiting (60% vs. 10%), diarrhea (50% vs. 21%), fatigue/asthenia (44% vs. 25%), constipation (39% vs. 24%), pneumonia (27% vs. 17%), abdominal pain (22% vs. 13%) arthralgia (14% vs. 10%), decreased appetite (13% vs. 6%), febrile neutropenia (12% vs. 8%), dizziness (11% vs. 9%), and pain in extremity (11% vs. 5%). Permanent discontinuation because of an adverse reaction occurred in 8% of patients.
 

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

Clinical data for the first-ever RET inhibitor, selpercatinib (Retevmo), show efficacy in two groups of patients with cancer – those with RET fusion–positive non–small cell lung cancer (NSCLC), and those with RET-mutant medullary thyroid cancer (MTC).

The drug showed “very good efficacy and also very good tolerability” in both groups, said lead author Lori J. Wirth, MD, medical director of head and neck cancers, Massachusetts General Hospital Cancer Center, Boston, in a statement.

“The response rates are high, responses are very durable, and overall, the drug does not cause a lot of toxicity,” she said.

“If you have a clean, RET-specific inhibitor such as selpercatinib, then you can really pound down RET very strongly and hit the driver alteration much harder, with a better side effect profile,” Dr. Wirth added.

Both groups of patients were part of the phase 1/2 LIBRETTO-001 study, which served as the basis for the recent accelerated approval of selpercatinib by the Food and Drug Administration.

Data from LIBRETTO-001 were published in the New England Journal of Medicine as two articles, one on NSCLC patients and one on MTC patients.

There has been a “remarkable increase” in the number of targeted agents that are effective in treating patients with advanced cancers that harbor specific genomic alterations, commented Razelle Kurzrock, MD, from the University of California, San Diego, in an accompanying editorial.

Selpercatinib, a potent RET inhibitor, “is now poised to alter the landscape of another genomic subgroup – RET-altered cancers,” she wrote.

Multikinase inhibitors such as vandetanib and cabozantinib have ancillary RET-inhibitor activity and are also active against RET-driven cancers. But these drugs are limited by off-target side effects, Dr. Krurzrock pointed out. “In contrast, next-generation, highly potent, and selective RET inhibitors such as selpercatinib offer the potential for improved efficacy and a more satisfactory side effect profile.”

In both parts of the study, selpercatinib produced durable responses in a majority of patients. Only about 3% of patients discontinued taking selpercatinib because of drug-related adverse events.

Taken together, these results show that selpercatinib “had marked and durable antitumor activity in most patients with RET-altered thyroid cancer or NSCLC,” wrote Dr. Krurzrock. “RET abnormalities now join other genomic alterations such as NTRK fusions, tumor mutational burden, and deficient mismatchrepair genes across cancers and ALK, BRAF, EGFR, MET, and ROS1 alterations in NSCLC that warrant molecular screening strategies.”

Results in patients with RET-mutated NSCLC

All patients enrolled in the LIBRETTO-001 trial received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

Of 105 patients with NSCLC who had received at least one platinum-based chemotherapy regimen, the objective response rate was 64%. The median duration of response was 17.5 months.

At a median follow-up of 12.1 months, 63% of the responses were ongoing.

The cohort included 39 treatment-naive patients, among whom the response rate was even higher, at 85%; 90% of the responses were ongoing at 6 months. In addition, 11 patients had measurable central nervous system metastasis at study enrollment. Of this group, 91% achieved an intracranial response.

Common adverse events of grade 3 or higher included hypertension (in 14% of the patients), an increase in ALT level (in 12%), an increase in AST level (in 10%), hyponatremia (in 6%), and lymphopenia (in 6%). The drug was discontinued in 12 patients because of a drug-related adverse event.
 

Results in patients with RET-mutated MTC

Efficacy for MTC was evaluated in 55 patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The objective response rate was 69%. The 1-year progression-free survival rate was 82%.

For the 88 patients who had not previously received vandetanib or cabozantinib, the response rate was 73%. The 1-year progression-free survival rate was 92%.

In a subgroup of 19 patients with previously treated RET fusion–positive thyroid cancer, 79% responded to the therapy; 1-year progression-free survival was 64%.

The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), an increase in ALT level (in 11%), an increase in AST level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Selpercatinib was discontinued by 12 patients because of drug-related adverse events.

The study was funded by Loxo Oncology (a wholly owned subsidiary of Eli Lilly) and by grants from the National Institutes of Health and the University of Texas MD Anderson Cancer Center. Kurzrock and Wirth report relationships with numerous pharmaceutical companies, as listed in the journal article.

This article first appeared on Medscape.com.

Clinical data for the first-ever RET inhibitor, selpercatinib (Retevmo), show efficacy in two groups of patients with cancer – those with RET fusion–positive non–small cell lung cancer (NSCLC), and those with RET-mutant medullary thyroid cancer (MTC).

The drug showed “very good efficacy and also very good tolerability” in both groups, said lead author Lori J. Wirth, MD, medical director of head and neck cancers, Massachusetts General Hospital Cancer Center, Boston, in a statement.

“The response rates are high, responses are very durable, and overall, the drug does not cause a lot of toxicity,” she said.

“If you have a clean, RET-specific inhibitor such as selpercatinib, then you can really pound down RET very strongly and hit the driver alteration much harder, with a better side effect profile,” Dr. Wirth added.

Both groups of patients were part of the phase 1/2 LIBRETTO-001 study, which served as the basis for the recent accelerated approval of selpercatinib by the Food and Drug Administration.

Data from LIBRETTO-001 were published in the New England Journal of Medicine as two articles, one on NSCLC patients and one on MTC patients.

There has been a “remarkable increase” in the number of targeted agents that are effective in treating patients with advanced cancers that harbor specific genomic alterations, commented Razelle Kurzrock, MD, from the University of California, San Diego, in an accompanying editorial.

Selpercatinib, a potent RET inhibitor, “is now poised to alter the landscape of another genomic subgroup – RET-altered cancers,” she wrote.

Multikinase inhibitors such as vandetanib and cabozantinib have ancillary RET-inhibitor activity and are also active against RET-driven cancers. But these drugs are limited by off-target side effects, Dr. Krurzrock pointed out. “In contrast, next-generation, highly potent, and selective RET inhibitors such as selpercatinib offer the potential for improved efficacy and a more satisfactory side effect profile.”

In both parts of the study, selpercatinib produced durable responses in a majority of patients. Only about 3% of patients discontinued taking selpercatinib because of drug-related adverse events.

Taken together, these results show that selpercatinib “had marked and durable antitumor activity in most patients with RET-altered thyroid cancer or NSCLC,” wrote Dr. Krurzrock. “RET abnormalities now join other genomic alterations such as NTRK fusions, tumor mutational burden, and deficient mismatchrepair genes across cancers and ALK, BRAF, EGFR, MET, and ROS1 alterations in NSCLC that warrant molecular screening strategies.”

Results in patients with RET-mutated NSCLC

All patients enrolled in the LIBRETTO-001 trial received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

Of 105 patients with NSCLC who had received at least one platinum-based chemotherapy regimen, the objective response rate was 64%. The median duration of response was 17.5 months.

At a median follow-up of 12.1 months, 63% of the responses were ongoing.

The cohort included 39 treatment-naive patients, among whom the response rate was even higher, at 85%; 90% of the responses were ongoing at 6 months. In addition, 11 patients had measurable central nervous system metastasis at study enrollment. Of this group, 91% achieved an intracranial response.

Common adverse events of grade 3 or higher included hypertension (in 14% of the patients), an increase in ALT level (in 12%), an increase in AST level (in 10%), hyponatremia (in 6%), and lymphopenia (in 6%). The drug was discontinued in 12 patients because of a drug-related adverse event.
 

Results in patients with RET-mutated MTC

Efficacy for MTC was evaluated in 55 patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The objective response rate was 69%. The 1-year progression-free survival rate was 82%.

For the 88 patients who had not previously received vandetanib or cabozantinib, the response rate was 73%. The 1-year progression-free survival rate was 92%.

In a subgroup of 19 patients with previously treated RET fusion–positive thyroid cancer, 79% responded to the therapy; 1-year progression-free survival was 64%.

The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), an increase in ALT level (in 11%), an increase in AST level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Selpercatinib was discontinued by 12 patients because of drug-related adverse events.

The study was funded by Loxo Oncology (a wholly owned subsidiary of Eli Lilly) and by grants from the National Institutes of Health and the University of Texas MD Anderson Cancer Center. Kurzrock and Wirth report relationships with numerous pharmaceutical companies, as listed in the journal article.

This article first appeared on Medscape.com.

Clinical data for the first-ever RET inhibitor, selpercatinib (Retevmo), show efficacy in two groups of patients with cancer – those with RET fusion–positive non–small cell lung cancer (NSCLC), and those with RET-mutant medullary thyroid cancer (MTC).

The drug showed “very good efficacy and also very good tolerability” in both groups, said lead author Lori J. Wirth, MD, medical director of head and neck cancers, Massachusetts General Hospital Cancer Center, Boston, in a statement.

“The response rates are high, responses are very durable, and overall, the drug does not cause a lot of toxicity,” she said.

“If you have a clean, RET-specific inhibitor such as selpercatinib, then you can really pound down RET very strongly and hit the driver alteration much harder, with a better side effect profile,” Dr. Wirth added.

Both groups of patients were part of the phase 1/2 LIBRETTO-001 study, which served as the basis for the recent accelerated approval of selpercatinib by the Food and Drug Administration.

Data from LIBRETTO-001 were published in the New England Journal of Medicine as two articles, one on NSCLC patients and one on MTC patients.

There has been a “remarkable increase” in the number of targeted agents that are effective in treating patients with advanced cancers that harbor specific genomic alterations, commented Razelle Kurzrock, MD, from the University of California, San Diego, in an accompanying editorial.

Selpercatinib, a potent RET inhibitor, “is now poised to alter the landscape of another genomic subgroup – RET-altered cancers,” she wrote.

Multikinase inhibitors such as vandetanib and cabozantinib have ancillary RET-inhibitor activity and are also active against RET-driven cancers. But these drugs are limited by off-target side effects, Dr. Krurzrock pointed out. “In contrast, next-generation, highly potent, and selective RET inhibitors such as selpercatinib offer the potential for improved efficacy and a more satisfactory side effect profile.”

In both parts of the study, selpercatinib produced durable responses in a majority of patients. Only about 3% of patients discontinued taking selpercatinib because of drug-related adverse events.

Taken together, these results show that selpercatinib “had marked and durable antitumor activity in most patients with RET-altered thyroid cancer or NSCLC,” wrote Dr. Krurzrock. “RET abnormalities now join other genomic alterations such as NTRK fusions, tumor mutational burden, and deficient mismatchrepair genes across cancers and ALK, BRAF, EGFR, MET, and ROS1 alterations in NSCLC that warrant molecular screening strategies.”

Results in patients with RET-mutated NSCLC

All patients enrolled in the LIBRETTO-001 trial received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

Of 105 patients with NSCLC who had received at least one platinum-based chemotherapy regimen, the objective response rate was 64%. The median duration of response was 17.5 months.

At a median follow-up of 12.1 months, 63% of the responses were ongoing.

The cohort included 39 treatment-naive patients, among whom the response rate was even higher, at 85%; 90% of the responses were ongoing at 6 months. In addition, 11 patients had measurable central nervous system metastasis at study enrollment. Of this group, 91% achieved an intracranial response.

Common adverse events of grade 3 or higher included hypertension (in 14% of the patients), an increase in ALT level (in 12%), an increase in AST level (in 10%), hyponatremia (in 6%), and lymphopenia (in 6%). The drug was discontinued in 12 patients because of a drug-related adverse event.
 

Results in patients with RET-mutated MTC

Efficacy for MTC was evaluated in 55 patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The objective response rate was 69%. The 1-year progression-free survival rate was 82%.

For the 88 patients who had not previously received vandetanib or cabozantinib, the response rate was 73%. The 1-year progression-free survival rate was 92%.

In a subgroup of 19 patients with previously treated RET fusion–positive thyroid cancer, 79% responded to the therapy; 1-year progression-free survival was 64%.

The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), an increase in ALT level (in 11%), an increase in AST level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Selpercatinib was discontinued by 12 patients because of drug-related adverse events.

The study was funded by Loxo Oncology (a wholly owned subsidiary of Eli Lilly) and by grants from the National Institutes of Health and the University of Texas MD Anderson Cancer Center. Kurzrock and Wirth report relationships with numerous pharmaceutical companies, as listed in the journal article.

This article first appeared on Medscape.com.

New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.

But yearly mammography between the ages of 40 and 49 years was associated with a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.

The researchers calculated that 1,150 women needed to undergo screening in the age group of 40-49 years to prevent 1 breast cancer death, or about 1 breast cancer death prevented per 1,000 screened.

However, they also noted that, in the years since the trial first began, there have been improvements in the treatment of breast cancer, so “there might be less scope for screening to reduce mortality in our current era.”

The study was published online August 12 in Lancet Oncology.

“Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis,” said lead author Stephen W. Duffy, MSc, director of the policy research unit in cancer awareness, screening and early diagnosis, at Queen Mary University, London.

That said, Dr. Duffy explained they do not expect policy makers to extend the age range on the basis of these results alone. “For one thing, they will want to consider costs, both human and financial.” “For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and, at this time, it would be impractical to try to expand the eligibility for screening.”

“I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over,” he added.
 

Guideline recommendations differ

Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.

The U.S. Preventive Services Task Force and American College of Physicians recommend screening every other year, on average, for women between the ages of 50 and 74 years.

However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing “as long as they are in good health.”

In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.

Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.

Results from the study’s 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).

In the current study, Dr. Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.

The cohort included 160,921 women enrolled between Oct. 14, 1990, and Sept. 24, 1997, who were randomized to screening (n = 53,883) or the control group (n = 106,953).

Of those screened during the study period, 7,893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.

At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; relative risk, 0.75; P = .029).

However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% confidence interval, 0.79-1.22; P = .86), the authors note.

“This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened,” commented Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England.

“In those first 10 years, out of every 10,000 women invited for screening, on average, about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average, 21 died. These numbers indicate that lives were saved,” he said.

“But they also indicate that death from breast cancer was pretty rare in women of that age,” he pointed out.

“Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women,” he said.

“Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is 6 deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate [1 death per 10,000 women] in those who had the screening,” Dr. McConway explained.

“But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1,150 women would have to be screened in their 40s to prevent one breast cancer death,” he noted.
 

U.S. experts support starting screening at 40

“The American Society of Breast Surgeons has continued to recommend screening women at the age of 40,” said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York. “There is no question that screening earlier saves more lives, and this study adds to the body of evidence already available.”

She pointed out that the argument against early screening was that there were many false positives, which, in turn, increased cost and anxiety. “Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount. Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic.”

Catherine Tuite, MD, section chief, breast radiology, Fox Chase Cancer Center, Philadelphia, echoed a similar viewpoint. “There is no real debate on this issue. The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women’s lives.”

She emphasized that these recommendations were made without the input of expert physicians. “The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40. We know that one-sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer.

“The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years,” she continued.

As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.

Dr. Duffy commented that, in the United Kingdom, the current screening protocol for mammograms is every 3 years, which he said “works well in women over the age of 50 years.” But for younger women, more frequent screening would be need – in this study, screening was done annually.

“The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women,” he said. “Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic.”

The study was funded by the Health Technology Assessment program of the National Institute for Health Research. Dr. Duffy reported also receiving grants from the NIHR outside this trial. Dr. Bernik, Dr. Tuite, and Dr. Hodgson reported no relevant financial relationships.

This article first appeared on Medscape.com.

New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.

But yearly mammography between the ages of 40 and 49 years was associated with a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.

The researchers calculated that 1,150 women needed to undergo screening in the age group of 40-49 years to prevent 1 breast cancer death, or about 1 breast cancer death prevented per 1,000 screened.

However, they also noted that, in the years since the trial first began, there have been improvements in the treatment of breast cancer, so “there might be less scope for screening to reduce mortality in our current era.”

The study was published online August 12 in Lancet Oncology.

“Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis,” said lead author Stephen W. Duffy, MSc, director of the policy research unit in cancer awareness, screening and early diagnosis, at Queen Mary University, London.

That said, Dr. Duffy explained they do not expect policy makers to extend the age range on the basis of these results alone. “For one thing, they will want to consider costs, both human and financial.” “For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and, at this time, it would be impractical to try to expand the eligibility for screening.”

“I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over,” he added.
 

Guideline recommendations differ

Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.

The U.S. Preventive Services Task Force and American College of Physicians recommend screening every other year, on average, for women between the ages of 50 and 74 years.

However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing “as long as they are in good health.”

In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.

Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.

Results from the study’s 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).

In the current study, Dr. Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.

The cohort included 160,921 women enrolled between Oct. 14, 1990, and Sept. 24, 1997, who were randomized to screening (n = 53,883) or the control group (n = 106,953).

Of those screened during the study period, 7,893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.

At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; relative risk, 0.75; P = .029).

However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% confidence interval, 0.79-1.22; P = .86), the authors note.

“This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened,” commented Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England.

“In those first 10 years, out of every 10,000 women invited for screening, on average, about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average, 21 died. These numbers indicate that lives were saved,” he said.

“But they also indicate that death from breast cancer was pretty rare in women of that age,” he pointed out.

“Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women,” he said.

“Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is 6 deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate [1 death per 10,000 women] in those who had the screening,” Dr. McConway explained.

“But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1,150 women would have to be screened in their 40s to prevent one breast cancer death,” he noted.
 

U.S. experts support starting screening at 40

“The American Society of Breast Surgeons has continued to recommend screening women at the age of 40,” said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York. “There is no question that screening earlier saves more lives, and this study adds to the body of evidence already available.”

She pointed out that the argument against early screening was that there were many false positives, which, in turn, increased cost and anxiety. “Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount. Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic.”

Catherine Tuite, MD, section chief, breast radiology, Fox Chase Cancer Center, Philadelphia, echoed a similar viewpoint. “There is no real debate on this issue. The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women’s lives.”

She emphasized that these recommendations were made without the input of expert physicians. “The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40. We know that one-sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer.

“The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years,” she continued.

As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.

Dr. Duffy commented that, in the United Kingdom, the current screening protocol for mammograms is every 3 years, which he said “works well in women over the age of 50 years.” But for younger women, more frequent screening would be need – in this study, screening was done annually.

“The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women,” he said. “Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic.”

The study was funded by the Health Technology Assessment program of the National Institute for Health Research. Dr. Duffy reported also receiving grants from the NIHR outside this trial. Dr. Bernik, Dr. Tuite, and Dr. Hodgson reported no relevant financial relationships.

This article first appeared on Medscape.com.

New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.

But yearly mammography between the ages of 40 and 49 years was associated with a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.

The researchers calculated that 1,150 women needed to undergo screening in the age group of 40-49 years to prevent 1 breast cancer death, or about 1 breast cancer death prevented per 1,000 screened.

However, they also noted that, in the years since the trial first began, there have been improvements in the treatment of breast cancer, so “there might be less scope for screening to reduce mortality in our current era.”

The study was published online August 12 in Lancet Oncology.

“Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis,” said lead author Stephen W. Duffy, MSc, director of the policy research unit in cancer awareness, screening and early diagnosis, at Queen Mary University, London.

That said, Dr. Duffy explained they do not expect policy makers to extend the age range on the basis of these results alone. “For one thing, they will want to consider costs, both human and financial.” “For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and, at this time, it would be impractical to try to expand the eligibility for screening.”

“I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over,” he added.
 

Guideline recommendations differ

Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.

The U.S. Preventive Services Task Force and American College of Physicians recommend screening every other year, on average, for women between the ages of 50 and 74 years.

However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing “as long as they are in good health.”

In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.

Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.

Results from the study’s 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).

In the current study, Dr. Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.

The cohort included 160,921 women enrolled between Oct. 14, 1990, and Sept. 24, 1997, who were randomized to screening (n = 53,883) or the control group (n = 106,953).

Of those screened during the study period, 7,893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.

At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; relative risk, 0.75; P = .029).

However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% confidence interval, 0.79-1.22; P = .86), the authors note.

“This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened,” commented Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England.

“In those first 10 years, out of every 10,000 women invited for screening, on average, about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average, 21 died. These numbers indicate that lives were saved,” he said.

“But they also indicate that death from breast cancer was pretty rare in women of that age,” he pointed out.

“Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women,” he said.

“Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is 6 deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate [1 death per 10,000 women] in those who had the screening,” Dr. McConway explained.

“But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1,150 women would have to be screened in their 40s to prevent one breast cancer death,” he noted.
 

U.S. experts support starting screening at 40

“The American Society of Breast Surgeons has continued to recommend screening women at the age of 40,” said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York. “There is no question that screening earlier saves more lives, and this study adds to the body of evidence already available.”

She pointed out that the argument against early screening was that there were many false positives, which, in turn, increased cost and anxiety. “Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount. Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic.”

Catherine Tuite, MD, section chief, breast radiology, Fox Chase Cancer Center, Philadelphia, echoed a similar viewpoint. “There is no real debate on this issue. The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women’s lives.”

She emphasized that these recommendations were made without the input of expert physicians. “The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40. We know that one-sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer.

“The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years,” she continued.

As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.

Dr. Duffy commented that, in the United Kingdom, the current screening protocol for mammograms is every 3 years, which he said “works well in women over the age of 50 years.” But for younger women, more frequent screening would be need – in this study, screening was done annually.

“The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women,” he said. “Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic.”

The study was funded by the Health Technology Assessment program of the National Institute for Health Research. Dr. Duffy reported also receiving grants from the NIHR outside this trial. Dr. Bernik, Dr. Tuite, and Dr. Hodgson reported no relevant financial relationships.

This article first appeared on Medscape.com.

A new test, the first to combine liquid biopsy and next-generation sequencing (NGS), has been approved by the US Food and Drug Administration (FDA) for use in patients with metastatic non–small cell lung cancer (NSCLC) to identify tumors with specific mutation types of the epidermal growth factor receptor (EGFR) gene.

The Guardant360 CDx assay (Guardant Health) is the first to combine the two technologies into a diagnostic test to guide treatment decisions.

Liquid biopsy offers the advantage of obtaining genetic information on a tumor from a simple blood draw instead of a tissue biopsy, which requires fine-needle aspiration of the lung. “ It is less invasive and more easily repeatable in comparison to standard tissue biopsies ... and can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor,” the FDA commented.

NGS offers the advantage of simultaneously detecting mutations in 55 tumor genes, as opposed to conducting a separate test for each gene.

However, although the assay can provide information on multiple solid tumor biomarkers, the approval is specific only to identifying EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso, AstraZeneca).

The approval does not validate the test for use in detecting other biomarkers, the FDA noted.

As previously reported, the assay has a comprehensive NGS panel that identifies seven guideline-recommended predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) — known as the G7 biomarkers — and one prognostic marker (KRAS).

But the FDA noted that “genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval.

“If the specific NSCLC mutations associated with today’s approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present,” the agency emphasized.

Nevertheless, the FDA announcement highlights the potential of the test to identify these other biomarkers.

“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, commented in a statement. 

“In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms,” he noted.

The manufacturer also highlighted this potential. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx,” Helmy Eltoukhy, PhD, CEO of Guardant Health, said in a statement.

NILE Study

The FDA did not cite any specific trial of the assay in its announcement of the approval, but Medscape Medical News has previously reported results from the NILE study presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).

The NILE trial was conducted in 282 patients with untreated nonsquamous NSCLC who underwent standard-of-care tissue genotyping and had a pretreatment blood sample for cell-free DNA (cfDNA) analysis.

Results showed that a G7 biomarker was identified in a significantly higher proportion of liquid biopsies compared with tissue genotyping (27.3% vs 21.3%; P < .0001).

The lower frequency of G7 biomarkers in tissue genotyping was due to insufficient tissue for sequential sequencing, the authors reported at that time.

Liquid biopsy improved G7 detection frequency by 48%, from 60 to 89 patients, which included samples that were negative by tissue testing (7), not tested (16), or lacked sufficient sample for a tissue-based test (6).

Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 patients (12.4%) had an activating KRAS mutation identified in the tissue alone, and with cfDNA, KRAS-positivity increased from 24 to 92 patients.

The Guardant360 CDx assay has been granted a breakthrough device designation, whereby the FDA provides intensive interaction and guidance on efficient device development to the company.
 

This article first appeared on Medscape.com.

A new test, the first to combine liquid biopsy and next-generation sequencing (NGS), has been approved by the US Food and Drug Administration (FDA) for use in patients with metastatic non–small cell lung cancer (NSCLC) to identify tumors with specific mutation types of the epidermal growth factor receptor (EGFR) gene.

The Guardant360 CDx assay (Guardant Health) is the first to combine the two technologies into a diagnostic test to guide treatment decisions.

Liquid biopsy offers the advantage of obtaining genetic information on a tumor from a simple blood draw instead of a tissue biopsy, which requires fine-needle aspiration of the lung. “ It is less invasive and more easily repeatable in comparison to standard tissue biopsies ... and can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor,” the FDA commented.

NGS offers the advantage of simultaneously detecting mutations in 55 tumor genes, as opposed to conducting a separate test for each gene.

However, although the assay can provide information on multiple solid tumor biomarkers, the approval is specific only to identifying EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso, AstraZeneca).

The approval does not validate the test for use in detecting other biomarkers, the FDA noted.

As previously reported, the assay has a comprehensive NGS panel that identifies seven guideline-recommended predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) — known as the G7 biomarkers — and one prognostic marker (KRAS).

But the FDA noted that “genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval.

“If the specific NSCLC mutations associated with today’s approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present,” the agency emphasized.

Nevertheless, the FDA announcement highlights the potential of the test to identify these other biomarkers.

“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, commented in a statement. 

“In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms,” he noted.

The manufacturer also highlighted this potential. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx,” Helmy Eltoukhy, PhD, CEO of Guardant Health, said in a statement.

NILE Study

The FDA did not cite any specific trial of the assay in its announcement of the approval, but Medscape Medical News has previously reported results from the NILE study presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).

The NILE trial was conducted in 282 patients with untreated nonsquamous NSCLC who underwent standard-of-care tissue genotyping and had a pretreatment blood sample for cell-free DNA (cfDNA) analysis.

Results showed that a G7 biomarker was identified in a significantly higher proportion of liquid biopsies compared with tissue genotyping (27.3% vs 21.3%; P < .0001).

The lower frequency of G7 biomarkers in tissue genotyping was due to insufficient tissue for sequential sequencing, the authors reported at that time.

Liquid biopsy improved G7 detection frequency by 48%, from 60 to 89 patients, which included samples that were negative by tissue testing (7), not tested (16), or lacked sufficient sample for a tissue-based test (6).

Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 patients (12.4%) had an activating KRAS mutation identified in the tissue alone, and with cfDNA, KRAS-positivity increased from 24 to 92 patients.

The Guardant360 CDx assay has been granted a breakthrough device designation, whereby the FDA provides intensive interaction and guidance on efficient device development to the company.
 

This article first appeared on Medscape.com.

A new test, the first to combine liquid biopsy and next-generation sequencing (NGS), has been approved by the US Food and Drug Administration (FDA) for use in patients with metastatic non–small cell lung cancer (NSCLC) to identify tumors with specific mutation types of the epidermal growth factor receptor (EGFR) gene.

The Guardant360 CDx assay (Guardant Health) is the first to combine the two technologies into a diagnostic test to guide treatment decisions.

Liquid biopsy offers the advantage of obtaining genetic information on a tumor from a simple blood draw instead of a tissue biopsy, which requires fine-needle aspiration of the lung. “ It is less invasive and more easily repeatable in comparison to standard tissue biopsies ... and can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor,” the FDA commented.

NGS offers the advantage of simultaneously detecting mutations in 55 tumor genes, as opposed to conducting a separate test for each gene.

However, although the assay can provide information on multiple solid tumor biomarkers, the approval is specific only to identifying EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso, AstraZeneca).

The approval does not validate the test for use in detecting other biomarkers, the FDA noted.

As previously reported, the assay has a comprehensive NGS panel that identifies seven guideline-recommended predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) — known as the G7 biomarkers — and one prognostic marker (KRAS).

But the FDA noted that “genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval.

“If the specific NSCLC mutations associated with today’s approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present,” the agency emphasized.

Nevertheless, the FDA announcement highlights the potential of the test to identify these other biomarkers.

“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, commented in a statement. 

“In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms,” he noted.

The manufacturer also highlighted this potential. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx,” Helmy Eltoukhy, PhD, CEO of Guardant Health, said in a statement.

NILE Study

The FDA did not cite any specific trial of the assay in its announcement of the approval, but Medscape Medical News has previously reported results from the NILE study presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).

The NILE trial was conducted in 282 patients with untreated nonsquamous NSCLC who underwent standard-of-care tissue genotyping and had a pretreatment blood sample for cell-free DNA (cfDNA) analysis.

Results showed that a G7 biomarker was identified in a significantly higher proportion of liquid biopsies compared with tissue genotyping (27.3% vs 21.3%; P < .0001).

The lower frequency of G7 biomarkers in tissue genotyping was due to insufficient tissue for sequential sequencing, the authors reported at that time.

Liquid biopsy improved G7 detection frequency by 48%, from 60 to 89 patients, which included samples that were negative by tissue testing (7), not tested (16), or lacked sufficient sample for a tissue-based test (6).

Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 patients (12.4%) had an activating KRAS mutation identified in the tissue alone, and with cfDNA, KRAS-positivity increased from 24 to 92 patients.

The Guardant360 CDx assay has been granted a breakthrough device designation, whereby the FDA provides intensive interaction and guidance on efficient device development to the company.
 

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.

“We can’t say for sure that the patients didn’t have any symptoms, but we detected the cancer years before they ever walked into the hospital,” said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. “We were also able to follow up with patients, so we actually knew that they had cancer.”

Zhang noted that they also followed the individuals whose tests indicated they were cancer free. “They were healthy at the time the samples were obtained, and they remained healthy,” he said. “Follow-up was key to validating these data.”

The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.

The study was published online July 21 in Nature Communications.
 

Unique among tests

Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes, as well as eight protein biomarkers.

Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.

The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.

The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.
 

Study details

The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).

For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.

The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.

The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.

A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.

Zhang feels that initially it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. “For any test, it is always more prudent to begin with a high-risk population,” he said. “You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk.”

He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. “The option was to break it down to five different studies,” he said. “We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study.”
 

High bar to reach

Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is “quite a ways to go before this can be clinically actionable.

“A lot of us are looking at combining methylation with circulating tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these,” he said.

Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. “This is something that’s used to assess for minimal residual disease in patients who have undergone surgery and appear to be ‘cured’ of the disease,” he said. “The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind.”

The type of test that has piqued the most interest is one that is “tumor informed,” meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. “That is a very targeted way of surveillance,” said Weinberg, “But it would be very difficult to use a tumor-informed test on the population described in this study because you don’t know if there is going to be a tumor or not.”

The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. “If there is a positive finding, then which cancer do you look for?” he commented. “It has an issue in that regard, and that’s the problem with this type of test, as it is easier if there is one site of origin.”

Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.

“There would have to be a randomized trial, and the test will have to show a survival benefit,” Weinberg said. He noted that it can sometimes be challenging to do so.

“Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal,” he added. “And these are established tests, and they show how difficult this can be.”

The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.

This article first appeared on Medscape.com.

A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.

“We can’t say for sure that the patients didn’t have any symptoms, but we detected the cancer years before they ever walked into the hospital,” said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. “We were also able to follow up with patients, so we actually knew that they had cancer.”

Zhang noted that they also followed the individuals whose tests indicated they were cancer free. “They were healthy at the time the samples were obtained, and they remained healthy,” he said. “Follow-up was key to validating these data.”

The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.

The study was published online July 21 in Nature Communications.
 

Unique among tests

Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes, as well as eight protein biomarkers.

Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.

The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.

The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.
 

Study details

The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).

For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.

The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.

The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.

A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.

Zhang feels that initially it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. “For any test, it is always more prudent to begin with a high-risk population,” he said. “You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk.”

He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. “The option was to break it down to five different studies,” he said. “We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study.”
 

High bar to reach

Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is “quite a ways to go before this can be clinically actionable.

“A lot of us are looking at combining methylation with circulating tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these,” he said.

Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. “This is something that’s used to assess for minimal residual disease in patients who have undergone surgery and appear to be ‘cured’ of the disease,” he said. “The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind.”

The type of test that has piqued the most interest is one that is “tumor informed,” meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. “That is a very targeted way of surveillance,” said Weinberg, “But it would be very difficult to use a tumor-informed test on the population described in this study because you don’t know if there is going to be a tumor or not.”

The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. “If there is a positive finding, then which cancer do you look for?” he commented. “It has an issue in that regard, and that’s the problem with this type of test, as it is easier if there is one site of origin.”

Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.

“There would have to be a randomized trial, and the test will have to show a survival benefit,” Weinberg said. He noted that it can sometimes be challenging to do so.

“Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal,” he added. “And these are established tests, and they show how difficult this can be.”

The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.

This article first appeared on Medscape.com.

A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.

“We can’t say for sure that the patients didn’t have any symptoms, but we detected the cancer years before they ever walked into the hospital,” said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. “We were also able to follow up with patients, so we actually knew that they had cancer.”

Zhang noted that they also followed the individuals whose tests indicated they were cancer free. “They were healthy at the time the samples were obtained, and they remained healthy,” he said. “Follow-up was key to validating these data.”

The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.

The study was published online July 21 in Nature Communications.
 

Unique among tests

Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes, as well as eight protein biomarkers.

Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.

The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.

The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.
 

Study details

The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).

For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.

The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.

The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.

A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.

Zhang feels that initially it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. “For any test, it is always more prudent to begin with a high-risk population,” he said. “You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk.”

He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. “The option was to break it down to five different studies,” he said. “We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study.”
 

High bar to reach

Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is “quite a ways to go before this can be clinically actionable.

“A lot of us are looking at combining methylation with circulating tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these,” he said.

Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. “This is something that’s used to assess for minimal residual disease in patients who have undergone surgery and appear to be ‘cured’ of the disease,” he said. “The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind.”

The type of test that has piqued the most interest is one that is “tumor informed,” meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. “That is a very targeted way of surveillance,” said Weinberg, “But it would be very difficult to use a tumor-informed test on the population described in this study because you don’t know if there is going to be a tumor or not.”

The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. “If there is a positive finding, then which cancer do you look for?” he commented. “It has an issue in that regard, and that’s the problem with this type of test, as it is easier if there is one site of origin.”

Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.

“There would have to be a randomized trial, and the test will have to show a survival benefit,” Weinberg said. He noted that it can sometimes be challenging to do so.

“Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal,” he added. “And these are established tests, and they show how difficult this can be.”

The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.

This article first appeared on Medscape.com.

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has given a thumbs up to avapritinib and acalabrutinib, paving the way for the drugs’ approval in the European Union (EU). 

The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.

The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.

The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.

Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.

First targeted therapy for mutation

If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.

Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.

For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.

The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.

In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website. 

Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.

New treatment for CLL

Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year.  In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.

The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.

In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).

At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).

The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.

In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).

At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).

The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
 

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

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has given a thumbs up to avapritinib and acalabrutinib, paving the way for the drugs’ approval in the European Union (EU). 

The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.

The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.

The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.

Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.

First targeted therapy for mutation

If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.

Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.

For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.

The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.

In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website. 

Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.

New treatment for CLL

Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year.  In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.

The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.

In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).

At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).

The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.

In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).

At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).

The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
 

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

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has given a thumbs up to avapritinib and acalabrutinib, paving the way for the drugs’ approval in the European Union (EU). 

The CHMP recommended granting conditional marketing authorization for avapritinib (Ayvakit, Blueprint Medicines) for use in adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. About 6%-10% of GIST tumors harbor this mutation, and avapritinib is a selective and potent inhibitor of KIT and PDGFRA mutant kinases.

The CHMP also adopted a positive opinion for acalabrutinib (Calquence, AstraZeneca) for the treatment of chronic lymphocytic leukemia (CLL) as monotherapy in patients who are treatment-naive or have received at least one prior therapy.

The CHMP opinion on both drugs will be reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the EU.

Detailed recommendations for the use of both drugs will be provided in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the products receive marketing authorization by the European Commission.

First targeted therapy for mutation

If approved by the European Commission, avapritinib would be the first treatment in the EU indicated for patients with PDGFRA D842V-mutant GIST.

Avapritinib was approved by the US Food and Drug Administration (FDA) earlier this year for the aforementioned indication. The FDA approval was based on findings from the phase 1 NAVIGATOR trial, which included 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with the most common mutation, PDGFRA D842V.

For patients harboring a PDGFRA exon 18 mutation, the overall response rate (ORR) was 84%, with 7% having a complete response and 77% having a partial response. Patients with the PDGFRA D842V mutation achieved an ORR of 89%, with 8% having a complete response and 82% having a partial response.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies ... Today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, in a statement at the time of approval.

The most common side effects (≥ 20% of patients) observed in patients taking avapritinib include nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite, and memory impairment. There may also be a risk of intracranial hemorrhage, in which case the dose should be reduced or the drug should be discontinued.

In the EU, conditional marketing authorization is granted to a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required, the CHMP notes on its website. 

Avapritinib had received an orphan medicine designation during development, which the EMA will review to determine if the designation can be maintained.

New treatment for CLL

Acalabrutinib is already approved in the United States, Canada, and Australia for the treatment of CLL and small lymphocytic lymphoma. The product was approved at the same time by all three regulatory authorities last year.  In the United States, acalabrutinib had previously been approved for use in mantle cell lymphoma.

The CHMP’s positive opinion of acalabrutinib is based on results from two phase 3 trials, ELEVATE TN and ASCEND.

In the ASCEND trial, acalabrutinib was compared with investigator’s choice of idelalisib or bendamustine with rituximab. The trial, which involved 310 patients with relapsed/refractory CLL, showed that acalabrutinib improved progression-free survival (PFS).

At a median follow-up of 16.1 months, the median PFS was not reached with acalabrutinib and was 16.5 months with investigator’s choice of therapy (P < .0001).

The most commonly reported adverse events seen with acalabrutinib were respiratory tract infections, headache, bruising, contusion, diarrhea, nausea, rash, musculoskeletal pain, fatigue, decreased hemoglobin, and decreased platelets.

In the ELEVATE TN trial, acalabrutinib was given alone or combined with obinutuzumab and compared to chlorambucil plus obinutuzumab in patients with previously untreated CLL. There were 535 patients randomized to receive acalabrutinib alone (n = 179), acalabrutinib plus obinutuzumab (n = 179), and chlorambucil plus obinutuzumab (n = 177).

At a median follow-up of 28 months, the median PFS was not reached with acalabrutinib alone or with acalabrutinib plus obinutuzumab, but the median PFS was 22.6 months in the chlorambucil-obinutuzumab arm (P < .0001 for both comparisons).

The most common adverse events in the acalabrutinib arms were headache, diarrhea, neutropenia, and nausea.
 

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

Most U.S. oncologists live within in their means and save their money, and a large proportion have a net worth of between $1 million and $5 million, according to the new Medscape Oncologist Debt and Net Worth Report 2020.

The average annual income for oncologists surveyed was $377,000, which was 5% higher than the $359,000 reported for 2018. This put oncologists in eleventh place among 29 specialties.

However, this information was obtained prior to February 11, 2020, before the COVID-19 pandemic took hold in the United States, and the financial situation has changed for many physicians.

For example, primary care physicians have reported a 55% decrease in revenue along with a 20% to 30% reduction in patient volume. The decline has even led some to shutter their physical offices, according to the larger survey of all physicians, the Medscape Physician Debt and Net Worth Report 2020. This full survey included 17, 461 physicians and represented 30 specialties.

Physicians in specialty practices may be facing even greater reductions. “Specialists are currently having more troubles than PCPs because they’re largely dependent on elective cases, which can’t be directly addressed by telemedicine,” commented Joel Greenwald, MD, CEO of Greenwald Wealth Management, St. Louis Park, Minnesota, in the survey.

Community oncology clinics and practices have reported a substantial decline in office visits and new patients because of the COVID-19 pandemic. Even before the pandemic, clinics had been closing in recent years as a result of being acquired, merging, or because of financial struggles, although that trend has been plateauing, according to the latest report from the Community Oncology Alliance.
 

Oncologists’ net worth

With regard to net worth, 42% of the oncologists surveyed reported having assets totaling from $1 million to $5 million, which is about the same for physicians in general. Only 15% reported a net worth of $5 million or higher; a quarter reported a net worth of less than $500,000.

Wealth is more evenly divided when it comes to gender in comparison with other specialties. For all physicians, 56% of men and 39% of women reported a net worth of more than $1 million. For oncologists, that ratio is 59% of men and 54% of women.

Not surprisingly, net worth also increased by age. Only about a quarter (27%) of oncologists younger than age 45 reported a net worth of $1 million to $5 million, compared to 48% aged 45-54 and 56% of physicians aged 55-64. This makes sense, inasmuch as earnings generally increase over time and early-career debt is paid down. However, net worth does appear to decline somewhat after the age of 65, presumably because of a decrease in income on retirement.
 

Debts and expenses

For debts and expenses that are currently being paid off, mortgage on a primary residence (59%) topped the list. More than half of oncologists reported living in a home that is 3,000 sq ft or larger, and nearly half (49%) have a mortgage of $300,000 or higher. About a third of the oncologists surveyed have no mortgage or one that has been paid off.

Car loan payments (35%) and college education/medical school loans (25%) were the second and third most common sources of debt. As compared with other specialties, oncologists land right in the middle of those still paying off school loans. Only 15% reported that they had no debts or expenses to be paid off.
 

Savings and living within one’s means

The average American has four credit cards. About half of oncologists surveyed reported having four or fewer, although about a fifth (22%) have seven or more. But the vast majority reported living within their means (49%) or below their means (46%). Only 6% reported living above their means.

Surveyed oncologists also reported putting money aside in a tax-deferred retirement account or college savings account. Almost half (48%) are putting aside more than $2000 every month, and 28% save from $1000 to $2000. A small percentage (8%) reported not doing this on a regular basis.

A smaller percentage (40%) responded that they put more than $2000 a month into a taxable retirement or college savings account; 18% reported not doing this on a regular basis. More than two thirds also reported either having a written budget or a mental one for their personal expenses.

In 2019, most oncologists (77%) did not experience a financial loss. For those who did, bad investments on the stock market (14%) were the main cause. A smaller number reported real estate losses, problems with their practice, or job loss.

Nearly half (49%) reported that they currently work with a financial planner or have done so in the past.

This article first appeared on Medscape.com.

Most U.S. oncologists live within in their means and save their money, and a large proportion have a net worth of between $1 million and $5 million, according to the new Medscape Oncologist Debt and Net Worth Report 2020.

The average annual income for oncologists surveyed was $377,000, which was 5% higher than the $359,000 reported for 2018. This put oncologists in eleventh place among 29 specialties.

However, this information was obtained prior to February 11, 2020, before the COVID-19 pandemic took hold in the United States, and the financial situation has changed for many physicians.

For example, primary care physicians have reported a 55% decrease in revenue along with a 20% to 30% reduction in patient volume. The decline has even led some to shutter their physical offices, according to the larger survey of all physicians, the Medscape Physician Debt and Net Worth Report 2020. This full survey included 17, 461 physicians and represented 30 specialties.

Physicians in specialty practices may be facing even greater reductions. “Specialists are currently having more troubles than PCPs because they’re largely dependent on elective cases, which can’t be directly addressed by telemedicine,” commented Joel Greenwald, MD, CEO of Greenwald Wealth Management, St. Louis Park, Minnesota, in the survey.

Community oncology clinics and practices have reported a substantial decline in office visits and new patients because of the COVID-19 pandemic. Even before the pandemic, clinics had been closing in recent years as a result of being acquired, merging, or because of financial struggles, although that trend has been plateauing, according to the latest report from the Community Oncology Alliance.
 

Oncologists’ net worth

With regard to net worth, 42% of the oncologists surveyed reported having assets totaling from $1 million to $5 million, which is about the same for physicians in general. Only 15% reported a net worth of $5 million or higher; a quarter reported a net worth of less than $500,000.

Wealth is more evenly divided when it comes to gender in comparison with other specialties. For all physicians, 56% of men and 39% of women reported a net worth of more than $1 million. For oncologists, that ratio is 59% of men and 54% of women.

Not surprisingly, net worth also increased by age. Only about a quarter (27%) of oncologists younger than age 45 reported a net worth of $1 million to $5 million, compared to 48% aged 45-54 and 56% of physicians aged 55-64. This makes sense, inasmuch as earnings generally increase over time and early-career debt is paid down. However, net worth does appear to decline somewhat after the age of 65, presumably because of a decrease in income on retirement.
 

Debts and expenses

For debts and expenses that are currently being paid off, mortgage on a primary residence (59%) topped the list. More than half of oncologists reported living in a home that is 3,000 sq ft or larger, and nearly half (49%) have a mortgage of $300,000 or higher. About a third of the oncologists surveyed have no mortgage or one that has been paid off.

Car loan payments (35%) and college education/medical school loans (25%) were the second and third most common sources of debt. As compared with other specialties, oncologists land right in the middle of those still paying off school loans. Only 15% reported that they had no debts or expenses to be paid off.
 

Savings and living within one’s means

The average American has four credit cards. About half of oncologists surveyed reported having four or fewer, although about a fifth (22%) have seven or more. But the vast majority reported living within their means (49%) or below their means (46%). Only 6% reported living above their means.

Surveyed oncologists also reported putting money aside in a tax-deferred retirement account or college savings account. Almost half (48%) are putting aside more than $2000 every month, and 28% save from $1000 to $2000. A small percentage (8%) reported not doing this on a regular basis.

A smaller percentage (40%) responded that they put more than $2000 a month into a taxable retirement or college savings account; 18% reported not doing this on a regular basis. More than two thirds also reported either having a written budget or a mental one for their personal expenses.

In 2019, most oncologists (77%) did not experience a financial loss. For those who did, bad investments on the stock market (14%) were the main cause. A smaller number reported real estate losses, problems with their practice, or job loss.

Nearly half (49%) reported that they currently work with a financial planner or have done so in the past.

This article first appeared on Medscape.com.

Most U.S. oncologists live within in their means and save their money, and a large proportion have a net worth of between $1 million and $5 million, according to the new Medscape Oncologist Debt and Net Worth Report 2020.

The average annual income for oncologists surveyed was $377,000, which was 5% higher than the $359,000 reported for 2018. This put oncologists in eleventh place among 29 specialties.

However, this information was obtained prior to February 11, 2020, before the COVID-19 pandemic took hold in the United States, and the financial situation has changed for many physicians.

For example, primary care physicians have reported a 55% decrease in revenue along with a 20% to 30% reduction in patient volume. The decline has even led some to shutter their physical offices, according to the larger survey of all physicians, the Medscape Physician Debt and Net Worth Report 2020. This full survey included 17, 461 physicians and represented 30 specialties.

Physicians in specialty practices may be facing even greater reductions. “Specialists are currently having more troubles than PCPs because they’re largely dependent on elective cases, which can’t be directly addressed by telemedicine,” commented Joel Greenwald, MD, CEO of Greenwald Wealth Management, St. Louis Park, Minnesota, in the survey.

Community oncology clinics and practices have reported a substantial decline in office visits and new patients because of the COVID-19 pandemic. Even before the pandemic, clinics had been closing in recent years as a result of being acquired, merging, or because of financial struggles, although that trend has been plateauing, according to the latest report from the Community Oncology Alliance.
 

Oncologists’ net worth

With regard to net worth, 42% of the oncologists surveyed reported having assets totaling from $1 million to $5 million, which is about the same for physicians in general. Only 15% reported a net worth of $5 million or higher; a quarter reported a net worth of less than $500,000.

Wealth is more evenly divided when it comes to gender in comparison with other specialties. For all physicians, 56% of men and 39% of women reported a net worth of more than $1 million. For oncologists, that ratio is 59% of men and 54% of women.

Not surprisingly, net worth also increased by age. Only about a quarter (27%) of oncologists younger than age 45 reported a net worth of $1 million to $5 million, compared to 48% aged 45-54 and 56% of physicians aged 55-64. This makes sense, inasmuch as earnings generally increase over time and early-career debt is paid down. However, net worth does appear to decline somewhat after the age of 65, presumably because of a decrease in income on retirement.
 

Debts and expenses

For debts and expenses that are currently being paid off, mortgage on a primary residence (59%) topped the list. More than half of oncologists reported living in a home that is 3,000 sq ft or larger, and nearly half (49%) have a mortgage of $300,000 or higher. About a third of the oncologists surveyed have no mortgage or one that has been paid off.

Car loan payments (35%) and college education/medical school loans (25%) were the second and third most common sources of debt. As compared with other specialties, oncologists land right in the middle of those still paying off school loans. Only 15% reported that they had no debts or expenses to be paid off.
 

Savings and living within one’s means

The average American has four credit cards. About half of oncologists surveyed reported having four or fewer, although about a fifth (22%) have seven or more. But the vast majority reported living within their means (49%) or below their means (46%). Only 6% reported living above their means.

Surveyed oncologists also reported putting money aside in a tax-deferred retirement account or college savings account. Almost half (48%) are putting aside more than $2000 every month, and 28% save from $1000 to $2000. A small percentage (8%) reported not doing this on a regular basis.

A smaller percentage (40%) responded that they put more than $2000 a month into a taxable retirement or college savings account; 18% reported not doing this on a regular basis. More than two thirds also reported either having a written budget or a mental one for their personal expenses.

In 2019, most oncologists (77%) did not experience a financial loss. For those who did, bad investments on the stock market (14%) were the main cause. A smaller number reported real estate losses, problems with their practice, or job loss.

Nearly half (49%) reported that they currently work with a financial planner or have done so in the past.

This article first appeared on Medscape.com.