Non-Hodgkin Lymphoma

For patients with relapsed/refractory follicular lymphoma (R/R FL), chimeric antigen responder (CAR) T-cell therapy offers the best chance of survival, despite its high rate of serious side effects and the need to travel to infusion centers. Alternatively, updated chemo+immunotherapy regimens and bispecific antibodies provide less rigorous but effective treatment options for low-risk patients who cannot tolerate or access CAR T.

“CAR T-cells offer patients with relapsed or refractory follicular lymphoma the most durable responses and improved chance of survival beyond all other available therapies. This holds true for a broad range of high-risk disease features in patients with relapsed or refractory FL. Furthermore, it accomplishes this with a single infusion, and a discrete toxicity that is predictable, reversible and manageable,” said Caron Jacobson, MD, MMSc, of the Dana-Farber Cancer Institute in Boston.

Presenting at the Great Debates & Updates Hematologic Malignancies conference, held April 5-6 in New York City, Dr. Jacobson argued that more patients with R/R FL should be treated with CAR T.

Dana-Farber Cancer Institute

NY Presbyterian Hospital, Weill Cornell Medicine

For patients with relapsed/refractory follicular lymphoma (R/R FL), chimeric antigen responder (CAR) T-cell therapy offers the best chance of survival, despite its high rate of serious side effects and the need to travel to infusion centers. Alternatively, updated chemo+immunotherapy regimens and bispecific antibodies provide less rigorous but effective treatment options for low-risk patients who cannot tolerate or access CAR T.

“CAR T-cells offer patients with relapsed or refractory follicular lymphoma the most durable responses and improved chance of survival beyond all other available therapies. This holds true for a broad range of high-risk disease features in patients with relapsed or refractory FL. Furthermore, it accomplishes this with a single infusion, and a discrete toxicity that is predictable, reversible and manageable,” said Caron Jacobson, MD, MMSc, of the Dana-Farber Cancer Institute in Boston.

Presenting at the Great Debates & Updates Hematologic Malignancies conference, held April 5-6 in New York City, Dr. Jacobson argued that more patients with R/R FL should be treated with CAR T.

Dana-Farber Cancer Institute

NY Presbyterian Hospital, Weill Cornell Medicine

For patients with relapsed/refractory follicular lymphoma (R/R FL), chimeric antigen responder (CAR) T-cell therapy offers the best chance of survival, despite its high rate of serious side effects and the need to travel to infusion centers. Alternatively, updated chemo+immunotherapy regimens and bispecific antibodies provide less rigorous but effective treatment options for low-risk patients who cannot tolerate or access CAR T.

“CAR T-cells offer patients with relapsed or refractory follicular lymphoma the most durable responses and improved chance of survival beyond all other available therapies. This holds true for a broad range of high-risk disease features in patients with relapsed or refractory FL. Furthermore, it accomplishes this with a single infusion, and a discrete toxicity that is predictable, reversible and manageable,” said Caron Jacobson, MD, MMSc, of the Dana-Farber Cancer Institute in Boston.

Presenting at the Great Debates & Updates Hematologic Malignancies conference, held April 5-6 in New York City, Dr. Jacobson argued that more patients with R/R FL should be treated with CAR T.

Dana-Farber Cancer Institute

NY Presbyterian Hospital, Weill Cornell Medicine

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

Early data suggested that several new multicancer early detection (MCED) tests in development show promise for identifying cancers that lack routine screening options.

Analyses presented during a session at the American Association for Cancer Research annual meeting, revealed that three new MCED tests — CanScan, MERCURY, and OncoSeek — could detect a range of cancers and recognize the tissue of origin with high accuracy. One — OncoSeek — could also provide an affordable cancer screening option for individuals living in lower-income countries.

The need for these noninvasive liquid biopsy tests that can accurately identify multiple cancer types with a single blood draw, especially cancers without routine screening strategies, is pressing. “We know that the current cancer standard of care screening will identify less than 50% of all cancers, while more than 50% of all cancer deaths occur in types of cancer with no recommended screening,” said co-moderator Marie E. Wood, MD, of the University of Colorado Anschutz Medical Campus, in Aurora, Colorado.

That being said, “the clinical utility of multicancer detection tests has not been established and we’re concerned about issues of overdiagnosis and overtreatment,” she noted.

The Early Data 

One new MCED test called CanScan, developed by Geneseeq Technology, uses plasma cell-free DNA fragment patterns to detect cancer signals as well as identify the tissue of origin across 13 cancer types.

Overall, the CanScan test covers cancer types that contribute to two thirds of new cancer cases and 74% of morality globally, said presenter Shanshan Yang, of Geneseeq Research Institute, in Nanjing, China.

However, only five of these cancer types have screening recommendations issued by the US Preventive Services Task Force (USPSTF), Dr. Yang added.

The interim data comes from an ongoing large-scale prospective study evaluating the MCED test in a cohort of asymptomatic individuals between ages 45 and 75 years with an average risk for cancer and no cancer-related symptoms on enrollment.

Patients at baseline had their blood collected for the CanScan test and subsequently received annual routine physical exams once a year for 3 consecutive years, with an additional 2 years of follow-up. 

The analysis included 3724 participants with analyzable samples at the data cutoff in September 2023. Among the 3724 participants, 29 had confirmed cancer diagnoses. Among these cases, 14 patients had their cancer confirmed through USPSTF recommended screening and 15 were detected through outside of standard USPSTF screening, such as a thyroid ultrasound, Dr. Yang explained.

Almost 90% of the cancers (26 of 29) were detected in the stage I or II, and eight (27.5%) were not one of the test’s 13 targeted cancer types.

The CanScan test had a sensitivity of 55.2%, identifying 16 of 29 of the patients with cancer, including 10 of 21 individuals with stage I (47.6%), and two of three with stage II (66.7%). 

The test had a high specificity of 97.9%, meaning out of 100 people screened, only two had false negative findings.

Among the 15 patients who had their cancer detected outside of USPSTF screening recommendations, eight (53.3%) were found using a CanScan test, including patients with liver and endometrial cancers.

Compared with a positive predictive value of (PPV) of 1.6% with screening or physical exam methods alone, the CanScan test had a PPV of 17.4%, Dr. Yang reported. 

“The MCED test holds significant potential for early cancer screening in asymptomatic populations,” Dr. Yang and colleagues concluded.

Another new MCED test called MERCURY, also developed by Geneseeq Technology and presented during the session, used a similar method to detect cancer signals and predict the tissue of origin across 13 cancer types.

The researchers initially validated the test using 3076 patients with cancer and 3477 healthy controls with a target specificity of 99%. In this group, researchers reported a sensitivity of 0.865 and a specificity of 0.989.

The team then performed an independent validation analysis with 1465 participants, 732 with cancer and 733 with no cancer, and confirmed a high sensitivity and specificity of 0.874 and 0.978, respectively. The sensitivity increased incrementally by cancer stage — 0.768 for stage I, 0.840 for stage II, 0.923 for stage III, and 0.971 for stage IV.

The test identified the tissue of origin with high accuracy, the researchers noted, but cautioned that the test needs “to be further validated in a prospective cohort study.”

MCED in Low-Income Settings

The session also featured findings on a new affordable MCED test called OncoSeek, which could provide greater access to cancer testing in low- and middle-income countries.

The OncoSeek algorithm identifies the presence of cancer using seven protein tumor markers alongside clinical information, such as gender and age. Like other tests, the test also predicts the possible tissue of origin.

The test can be run on clinical protein assay instruments that are already widely available, such as Roche cobas analyzer, Mao Mao, MD, PhD, the founder and CEO of SeekIn, of Shenzhen, China, told this news organization.

This “feature makes the test accessible worldwide, even in low- and middle-income countries,” he said. “These instruments are fully-automated and part of today’s clinical practice. Therefore, the test does not require additional infrastructure building and lab personal training.”

Another notable advantage: the OncoSeek test only costs about $20, compared with other MCED tests, which can cost anywhere from $200 to $1000.

To validate the technology in a large, diverse cohort, Dr. Mao and colleagues enrolled approximately 10,000 participants, including 2003 cancer cases and 7888 non-cancer cases.

Peripheral blood was collected from each participant and analyzed using a panel of the seven protein tumor markers — AFP, CA125, CA15-3, CA19-9, CA72-4, CEA, and CYFRA 21-1.

To reduce the risk for false positive findings, the team designed the OncoSeek algorithm to achieve a specificity of 93%. Dr. Mao and colleagues found a sensitivity of 51.7%, resulting in an overall accuracy of 84.6%.

The performance was consistent in additional validation cohorts in Brazil, China, and the United States, with sensitivities ranging from 39.0% to 77.6% for detecting nine common cancer types, including breast, colorectal, liver, lung, lymphoma, esophagus, ovary, pancreas, and stomach. The sensitivity for pancreatic cancer was at the high end of 77.6%.

The test could predict the tissue of origin in about two thirds of cases. 

Given its low cost, OncoSeek represents an affordable and accessible option for cancer screening, the authors concluded. 

Overall, “I think MCEDs have the potential to enhance cancer screening,” Dr. Wood told this news organization.

Still, questions remain about the optimal use of these tests, such as whether they are best for average-risk or higher risk populations, and how to integrate them into standard screening, she said. 

Dr. Wood also cautioned that the studies presented in the session represent early data, and it is likely that the numbers, such as sensitivity and specificity, will change with further prospective analyses.

And ultimately, these tests should complement, not replace, standard screening. “A negative testing should not be taken as a sign to avoid standard screening,” Dr. Wood said.

Dr. Yang is an employee of Geneseeq Technology, Inc., and Dr. Mao is an employee of SeekIn. Dr. Wood had no disclosures to report.

A version of this article appeared on Medscape.com.

Early data suggested that several new multicancer early detection (MCED) tests in development show promise for identifying cancers that lack routine screening options.

Analyses presented during a session at the American Association for Cancer Research annual meeting, revealed that three new MCED tests — CanScan, MERCURY, and OncoSeek — could detect a range of cancers and recognize the tissue of origin with high accuracy. One — OncoSeek — could also provide an affordable cancer screening option for individuals living in lower-income countries.

The need for these noninvasive liquid biopsy tests that can accurately identify multiple cancer types with a single blood draw, especially cancers without routine screening strategies, is pressing. “We know that the current cancer standard of care screening will identify less than 50% of all cancers, while more than 50% of all cancer deaths occur in types of cancer with no recommended screening,” said co-moderator Marie E. Wood, MD, of the University of Colorado Anschutz Medical Campus, in Aurora, Colorado.

That being said, “the clinical utility of multicancer detection tests has not been established and we’re concerned about issues of overdiagnosis and overtreatment,” she noted.

The Early Data 

One new MCED test called CanScan, developed by Geneseeq Technology, uses plasma cell-free DNA fragment patterns to detect cancer signals as well as identify the tissue of origin across 13 cancer types.

Overall, the CanScan test covers cancer types that contribute to two thirds of new cancer cases and 74% of morality globally, said presenter Shanshan Yang, of Geneseeq Research Institute, in Nanjing, China.

However, only five of these cancer types have screening recommendations issued by the US Preventive Services Task Force (USPSTF), Dr. Yang added.

The interim data comes from an ongoing large-scale prospective study evaluating the MCED test in a cohort of asymptomatic individuals between ages 45 and 75 years with an average risk for cancer and no cancer-related symptoms on enrollment.

Patients at baseline had their blood collected for the CanScan test and subsequently received annual routine physical exams once a year for 3 consecutive years, with an additional 2 years of follow-up. 

The analysis included 3724 participants with analyzable samples at the data cutoff in September 2023. Among the 3724 participants, 29 had confirmed cancer diagnoses. Among these cases, 14 patients had their cancer confirmed through USPSTF recommended screening and 15 were detected through outside of standard USPSTF screening, such as a thyroid ultrasound, Dr. Yang explained.

Almost 90% of the cancers (26 of 29) were detected in the stage I or II, and eight (27.5%) were not one of the test’s 13 targeted cancer types.

The CanScan test had a sensitivity of 55.2%, identifying 16 of 29 of the patients with cancer, including 10 of 21 individuals with stage I (47.6%), and two of three with stage II (66.7%). 

The test had a high specificity of 97.9%, meaning out of 100 people screened, only two had false negative findings.

Among the 15 patients who had their cancer detected outside of USPSTF screening recommendations, eight (53.3%) were found using a CanScan test, including patients with liver and endometrial cancers.

Compared with a positive predictive value of (PPV) of 1.6% with screening or physical exam methods alone, the CanScan test had a PPV of 17.4%, Dr. Yang reported. 

“The MCED test holds significant potential for early cancer screening in asymptomatic populations,” Dr. Yang and colleagues concluded.

Another new MCED test called MERCURY, also developed by Geneseeq Technology and presented during the session, used a similar method to detect cancer signals and predict the tissue of origin across 13 cancer types.

The researchers initially validated the test using 3076 patients with cancer and 3477 healthy controls with a target specificity of 99%. In this group, researchers reported a sensitivity of 0.865 and a specificity of 0.989.

The team then performed an independent validation analysis with 1465 participants, 732 with cancer and 733 with no cancer, and confirmed a high sensitivity and specificity of 0.874 and 0.978, respectively. The sensitivity increased incrementally by cancer stage — 0.768 for stage I, 0.840 for stage II, 0.923 for stage III, and 0.971 for stage IV.

The test identified the tissue of origin with high accuracy, the researchers noted, but cautioned that the test needs “to be further validated in a prospective cohort study.”

MCED in Low-Income Settings

The session also featured findings on a new affordable MCED test called OncoSeek, which could provide greater access to cancer testing in low- and middle-income countries.

The OncoSeek algorithm identifies the presence of cancer using seven protein tumor markers alongside clinical information, such as gender and age. Like other tests, the test also predicts the possible tissue of origin.

The test can be run on clinical protein assay instruments that are already widely available, such as Roche cobas analyzer, Mao Mao, MD, PhD, the founder and CEO of SeekIn, of Shenzhen, China, told this news organization.

This “feature makes the test accessible worldwide, even in low- and middle-income countries,” he said. “These instruments are fully-automated and part of today’s clinical practice. Therefore, the test does not require additional infrastructure building and lab personal training.”

Another notable advantage: the OncoSeek test only costs about $20, compared with other MCED tests, which can cost anywhere from $200 to $1000.

To validate the technology in a large, diverse cohort, Dr. Mao and colleagues enrolled approximately 10,000 participants, including 2003 cancer cases and 7888 non-cancer cases.

Peripheral blood was collected from each participant and analyzed using a panel of the seven protein tumor markers — AFP, CA125, CA15-3, CA19-9, CA72-4, CEA, and CYFRA 21-1.

To reduce the risk for false positive findings, the team designed the OncoSeek algorithm to achieve a specificity of 93%. Dr. Mao and colleagues found a sensitivity of 51.7%, resulting in an overall accuracy of 84.6%.

The performance was consistent in additional validation cohorts in Brazil, China, and the United States, with sensitivities ranging from 39.0% to 77.6% for detecting nine common cancer types, including breast, colorectal, liver, lung, lymphoma, esophagus, ovary, pancreas, and stomach. The sensitivity for pancreatic cancer was at the high end of 77.6%.

The test could predict the tissue of origin in about two thirds of cases. 

Given its low cost, OncoSeek represents an affordable and accessible option for cancer screening, the authors concluded. 

Overall, “I think MCEDs have the potential to enhance cancer screening,” Dr. Wood told this news organization.

Still, questions remain about the optimal use of these tests, such as whether they are best for average-risk or higher risk populations, and how to integrate them into standard screening, she said. 

Dr. Wood also cautioned that the studies presented in the session represent early data, and it is likely that the numbers, such as sensitivity and specificity, will change with further prospective analyses.

And ultimately, these tests should complement, not replace, standard screening. “A negative testing should not be taken as a sign to avoid standard screening,” Dr. Wood said.

Dr. Yang is an employee of Geneseeq Technology, Inc., and Dr. Mao is an employee of SeekIn. Dr. Wood had no disclosures to report.

A version of this article appeared on Medscape.com.

Early data suggested that several new multicancer early detection (MCED) tests in development show promise for identifying cancers that lack routine screening options.

Analyses presented during a session at the American Association for Cancer Research annual meeting, revealed that three new MCED tests — CanScan, MERCURY, and OncoSeek — could detect a range of cancers and recognize the tissue of origin with high accuracy. One — OncoSeek — could also provide an affordable cancer screening option for individuals living in lower-income countries.

The need for these noninvasive liquid biopsy tests that can accurately identify multiple cancer types with a single blood draw, especially cancers without routine screening strategies, is pressing. “We know that the current cancer standard of care screening will identify less than 50% of all cancers, while more than 50% of all cancer deaths occur in types of cancer with no recommended screening,” said co-moderator Marie E. Wood, MD, of the University of Colorado Anschutz Medical Campus, in Aurora, Colorado.

That being said, “the clinical utility of multicancer detection tests has not been established and we’re concerned about issues of overdiagnosis and overtreatment,” she noted.

The Early Data 

One new MCED test called CanScan, developed by Geneseeq Technology, uses plasma cell-free DNA fragment patterns to detect cancer signals as well as identify the tissue of origin across 13 cancer types.

Overall, the CanScan test covers cancer types that contribute to two thirds of new cancer cases and 74% of morality globally, said presenter Shanshan Yang, of Geneseeq Research Institute, in Nanjing, China.

However, only five of these cancer types have screening recommendations issued by the US Preventive Services Task Force (USPSTF), Dr. Yang added.

The interim data comes from an ongoing large-scale prospective study evaluating the MCED test in a cohort of asymptomatic individuals between ages 45 and 75 years with an average risk for cancer and no cancer-related symptoms on enrollment.

Patients at baseline had their blood collected for the CanScan test and subsequently received annual routine physical exams once a year for 3 consecutive years, with an additional 2 years of follow-up. 

The analysis included 3724 participants with analyzable samples at the data cutoff in September 2023. Among the 3724 participants, 29 had confirmed cancer diagnoses. Among these cases, 14 patients had their cancer confirmed through USPSTF recommended screening and 15 were detected through outside of standard USPSTF screening, such as a thyroid ultrasound, Dr. Yang explained.

Almost 90% of the cancers (26 of 29) were detected in the stage I or II, and eight (27.5%) were not one of the test’s 13 targeted cancer types.

The CanScan test had a sensitivity of 55.2%, identifying 16 of 29 of the patients with cancer, including 10 of 21 individuals with stage I (47.6%), and two of three with stage II (66.7%). 

The test had a high specificity of 97.9%, meaning out of 100 people screened, only two had false negative findings.

Among the 15 patients who had their cancer detected outside of USPSTF screening recommendations, eight (53.3%) were found using a CanScan test, including patients with liver and endometrial cancers.

Compared with a positive predictive value of (PPV) of 1.6% with screening or physical exam methods alone, the CanScan test had a PPV of 17.4%, Dr. Yang reported. 

“The MCED test holds significant potential for early cancer screening in asymptomatic populations,” Dr. Yang and colleagues concluded.

Another new MCED test called MERCURY, also developed by Geneseeq Technology and presented during the session, used a similar method to detect cancer signals and predict the tissue of origin across 13 cancer types.

The researchers initially validated the test using 3076 patients with cancer and 3477 healthy controls with a target specificity of 99%. In this group, researchers reported a sensitivity of 0.865 and a specificity of 0.989.

The team then performed an independent validation analysis with 1465 participants, 732 with cancer and 733 with no cancer, and confirmed a high sensitivity and specificity of 0.874 and 0.978, respectively. The sensitivity increased incrementally by cancer stage — 0.768 for stage I, 0.840 for stage II, 0.923 for stage III, and 0.971 for stage IV.

The test identified the tissue of origin with high accuracy, the researchers noted, but cautioned that the test needs “to be further validated in a prospective cohort study.”

MCED in Low-Income Settings

The session also featured findings on a new affordable MCED test called OncoSeek, which could provide greater access to cancer testing in low- and middle-income countries.

The OncoSeek algorithm identifies the presence of cancer using seven protein tumor markers alongside clinical information, such as gender and age. Like other tests, the test also predicts the possible tissue of origin.

The test can be run on clinical protein assay instruments that are already widely available, such as Roche cobas analyzer, Mao Mao, MD, PhD, the founder and CEO of SeekIn, of Shenzhen, China, told this news organization.

This “feature makes the test accessible worldwide, even in low- and middle-income countries,” he said. “These instruments are fully-automated and part of today’s clinical practice. Therefore, the test does not require additional infrastructure building and lab personal training.”

Another notable advantage: the OncoSeek test only costs about $20, compared with other MCED tests, which can cost anywhere from $200 to $1000.

To validate the technology in a large, diverse cohort, Dr. Mao and colleagues enrolled approximately 10,000 participants, including 2003 cancer cases and 7888 non-cancer cases.

Peripheral blood was collected from each participant and analyzed using a panel of the seven protein tumor markers — AFP, CA125, CA15-3, CA19-9, CA72-4, CEA, and CYFRA 21-1.

To reduce the risk for false positive findings, the team designed the OncoSeek algorithm to achieve a specificity of 93%. Dr. Mao and colleagues found a sensitivity of 51.7%, resulting in an overall accuracy of 84.6%.

The performance was consistent in additional validation cohorts in Brazil, China, and the United States, with sensitivities ranging from 39.0% to 77.6% for detecting nine common cancer types, including breast, colorectal, liver, lung, lymphoma, esophagus, ovary, pancreas, and stomach. The sensitivity for pancreatic cancer was at the high end of 77.6%.

The test could predict the tissue of origin in about two thirds of cases. 

Given its low cost, OncoSeek represents an affordable and accessible option for cancer screening, the authors concluded. 

Overall, “I think MCEDs have the potential to enhance cancer screening,” Dr. Wood told this news organization.

Still, questions remain about the optimal use of these tests, such as whether they are best for average-risk or higher risk populations, and how to integrate them into standard screening, she said. 

Dr. Wood also cautioned that the studies presented in the session represent early data, and it is likely that the numbers, such as sensitivity and specificity, will change with further prospective analyses.

And ultimately, these tests should complement, not replace, standard screening. “A negative testing should not be taken as a sign to avoid standard screening,” Dr. Wood said.

Dr. Yang is an employee of Geneseeq Technology, Inc., and Dr. Mao is an employee of SeekIn. Dr. Wood had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.