Anticancer drugs approved in the last 2 decades provide modest improvements in survival, according to research published in the Journal of Clinical Oncology.
When evaluated together, the drugs were associated with a roughly 3-month improvement in median progression-free survival (PFS) and overall survival (OS).
This study encompassed 124 anticancer drugs that were approved by the US Food and Drug Administration (FDA) between 2003 and 2021. The drugs were approved for a total of 374 indications — 255 for solid tumors and 119 for hematologic malignancies.
Most of the approvals were standard approvals (n=266). Of the 108 accelerated approvals, 58 were converted to full approvals, 12 were not, and 38 were pending at the time of analysis.
A majority of the clinical trials supporting the drug approvals were open-label (71.4%), phase 3 (63.6%), and concurrent randomized controlled trials (66.3%). Across all the trials, the median number of patients enrolled was 331 (range, 123-665).
The researchers evaluated outcome data from the 248 concurrent randomized controlled trials and found that 188 trials (75.8%) reported OS data and 203 trials (81.9%) reported PFS data.
Overall, the drugs were associated with statistically significant reductions in the risk of disease progression (hazard ratio [HR], 0.57; 95% CI, 0.54-0.60) and death (HR, 0.73; 95% CI, 0.72-0.75).
However, the drugs prolonged OS by a median of 2.80 months and prolonged PFS by a median of 3.30 months, compared with control treatments.
OS was significantly better for first-in-class drugs (HR, 0.71; 95% CI, 0.68-0.74) than for drugs that were not first in class (HR, 0.75; 95% CI, 0.73-0.77; P =.020). The median OS was significantly longer with immune regulators than with targeted agents or cytotoxic agents — 3.45 months, 3.00 months, and 2.10 months, respectively (P =.043).
The median PFS was lower with immune regulators and cytotoxic agents than with targeted agents — 2.50 months, 1.45 months, and 4.00 months, respectively (P <.001). And PFS was significantly better with small-molecule drugs (HR, 0.49; 95% CI, 0.46-0.53) than with other drugs (HR, 0.65; 95% CI, 0.61-0.69; P <.001).
Taking these findings together, the researchers concluded that cancer drugs recently approved by the FDA provide only “marginal” benefits in PFS and OS.
“The FDA and physicians must cautiously evaluate initial drug approvals with nonrobust clinical evidence, which may overestimate efficacy outcomes,” the researchers wrote.
Michaeli DT, Michaeli T. Overall survival, progression-free survival, and tumor response benefit supporting initial US Food and Drug Administration approval and indication extension of new cancer drugs, 2003-2021. J Clin Oncol. Published online August 3, 2022. doi:10.1200/JCO.22.00535