In a study reported in the Journal of Clinical Oncology, Michaeli and Michaeli described data supporting U.S. Food and Drug Administration (FDA) initial approval and subsequent indications for new cancer drugs from 2003 through 2021.
Study Details
Clinical trial evidence supporting approval for each drug’s indications was collected from the Drugs@FDA database for the period of 2003 to 2021. Hazard ratios for overall survival and progression-free survival and relative risks for tumor response were derived from meta-analysis. Heterogeneity was assessed using the I2 statistic.
Key Findings
A total of 124 new drugs were approved; 78 were approved in multiple indications, yielding a total of 374 indications. Among the 374 indications, 141 were for combination therapies, 255 were for solid cancers, 121 included biomarkers, and 182 were for first-line therapy.
Approval was most frequently supported by open-label (267 [71%]) phase III (238 [64%]) randomized controlled trials (248 [66%]), with a median of 331 enrolled patients (interquartile range [IQR] = 123–665 patients). Approximately one-third of indications were supported by single-arm phase II trials.
Among 234 randomized controlled trials with available data, hazard ratios for all indications were 0.73 (95% confidence interval [CI] = 0.72–0.75; I2 = 29.6% for heterogeneity) for overall survival and 0.57 (95% CI = 0.54–0.60; I2 = 90.6% for heterogeneity) for progression-free survival. New drugs increased patient survival by a median of 2.80 months (interquartile range [IQR] = 1.97–4.60 months) and progression-free survival by a median of 3.30 months (IQR = 1.50–5.58 months). The relative risk for tumor response was 1.38 (95% CI = 1.33–1.42; I2 = 80.7% for heterogeneity), with a median duration of response of 5.00 months (IQR = 2.70–8.70 months).
Initial indications were associated with better hazard ratios vs subsequent indications for overall survival (0.70 vs 0.73, 0.75, and 0.79 for second, third, and fourth indications, respectively; overall P = .023) and for progression-free survival (0.48 vs 0.54, 0.58, and 0.59; overall P =.018) and better relative risks for tumor response (1.76 vs 1.34, 1.51, and 1.27; overall P = .001).
Among the 374 indications, 108 (29%) received accelerated approval. Accelerated approval was significantly more common for original than subsequent indications (45% vs 23%, P = .003).
The investigators concluded, “New cancer drugs substantially reduce the risk of death and tumor progression, yet only marginally extend patient survival. The FDA, physicians, patients, and insurers must evaluate and decide on a drug’s safety and efficacy approval, pricing, coverage, and reimbursement on an indication-specific level.”
Daniel Tobias Michaeli, MS, of Heidelberg University, University Hospital Mannheim, Mannheim, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
