Most molecular-targeted cancer therapies show no ‘substantial’ benefit at approval
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Key takeaways:
- Only 29% of indications supported high-benefit genomic-based cancer treatments.
- Overall response rate before approval served as a primary endpoint for 55% of indications.
Fewer than one-third of recently approved molecular-targeted cancer therapies demonstrated “substantial patient benefits,” according to data published in JAMA Oncology.
Researchers placed an emphasis on a need for robust trials over retrospective or exploratory analyses to best generate meaningful and impactful data that can help improve care for patients with cancer.
Background, methods
Researchers conducted a cohort study to assess the validity of molecular targets and therapeutic benefits of FDA-approved genome-targeted cancer drugs.
The study included genome-targeted cancer drugs approved by the FDA between Jan. 1, 2015, and Dec. 31, 2022; researchers analyzed key characteristics of pivotal trials from FDA drug labels and trial reports, while including assessed outcomes.
Researchers assessed the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT), while also evaluating clinical benefit for respective approved indications using the ESMO-Magnitude of Clinical Benefit Scale.
The scale rated substantial clinical benefit as a grade A or B for curative intent and 4 or 5 for noncurative intent, with molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-Magnitude of Clinical Benefit Scale being rated as high-benefit genomic-based cancer treatments.
Results, next steps
Researchers analyzed 50 molecular-targeted drugs covering 84 indications — 45 (54%) of which were approved based on phase 1 or phase 2 data, 45 (54%) by single-arm pivotal trials and 48 (57%) based on subgroup analyses.
Over half of primary endpoints (55%) appeared to be overall response rate [median ORR, 57% (interquartile range, 40%-69%); median duration of response, 11.1 (interquartile range, 9.2-19.8) months].
Among the 84 pivotal trials, 38 (45%) had I-A ESCAT targetability and 32 (38%) had I-B targetability. Only 24 (29%) showed substantial clinical benefit through ESMO-Magnitude of Clinical Benefit Scale,
By combining the above ratings, 24 of the 84 indications (29%) appeared associated with high-benefit genomic-based cancer treatments.
Potential limitations include the study using the ESMO-Magnitude of Clinical Benefit Scale, which happens to share the same limitations as the trials that researchers evaluated. Additionally, researchers only evaluated trials that supported regulatory approvals.
“The results of this cohort study demonstrated that for new cancer drugs, clinical benefit frameworks like those developed by ESMO help to identify therapies and molecular targets that provide high clinical benefit,” Ariadna Tibau, MD, PhD, of Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote. “Although next-generation sequencing has helped personalize cancer therapy for a growing number of patients, robust trials supporting the drug approvals should still be preferred to retrospective, exploratory analyses, followed by required postapproval studies and monitoring.
“These data reinforce the need for continued engagement of all stakeholders in generating adequate data to enable highvalue cancer care for patients,” they added.
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