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TOPLINE:

One in 6 patients in phase 2 cancer trials received treatments that were eventually approved by the US Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.

METHODOLOGY:

• Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
• Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
• The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the "therapeutic proportion."
• A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).

TAKEAWAY:

• A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
• The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
• The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
• Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.

IN PRACTICE:

"By entering a phase 2 trial, a patient has a 1 in 6 chance of receiving a treatment that will later be approved for their condition," the authors wrote. "The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient's therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments."

In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, "If using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines," he wrote.

SOURCE:

This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in JNCI: Journal of the National Cancer Institute.

LIMITATIONS:

The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.

DISCLOSURES:

This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.