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Pivotal studies of pharmacotherapies approved by the US FDA for cancer treatment: a meta-analysis.

The oncologist 2026 Vol.31(5)

Chow R, Im JHB, Zimmermann C, Richards GC, Heneghan C

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[BACKGROUND] This study aimed to examine the number of FDA-approved cancer pharmacotherapies and analyse pivotal study characteristics over time, including sample sizes.

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APA Chow R, Im JHB, et al. (2026). Pivotal studies of pharmacotherapies approved by the US FDA for cancer treatment: a meta-analysis.. The oncologist, 31(5). https://doi.org/10.1093/oncolo/oyag125
MLA Chow R, et al.. "Pivotal studies of pharmacotherapies approved by the US FDA for cancer treatment: a meta-analysis.." The oncologist, vol. 31, no. 5, 2026.
PMID 41926737

Abstract

[BACKGROUND] This study aimed to examine the number of FDA-approved cancer pharmacotherapies and analyse pivotal study characteristics over time, including sample sizes.

[METHODS] We developed a web scraper to collate a cohort of FDA-approved cancer pharmacotherapies from 1953 until 31 December 2024. For each pharmacotherapy, details of pivotal studies leading to approval were recorded, including protocol and final sample size, study design, therapy type, and quality assessment using Cochrane Risk of Bias tools. We used regression analyses and discretization to identify trends in sample size. Type I error was set at 0.05.(Study protocol pre-registration: https://doi.org/10.17605/OSF.IO/KVA23).

[RESULTS] We identified 255 pharmacotherapies, supported by 306 pivotal studies; 125 (49%) were targeted pharmacotherapies, 61 (24%) chemotherapies, 47 (18%) immunotherapies, 21 (8%) hormonal therapies, and 1 (0.4%) other. The median sample size was 290 (IQR = 427); sample sizes increased in the 1990s (median = 407) and remained stable thereafter. Stratified analysis demonstrated smaller sample sizes for phase 1 and 2 studies before 1980, with no change in phase 3 studies. For 165 studies reporting protocol sample sizes, studies from 2020-2024 (median = 147.5) were smaller than those from 2010-2019 (median = 320).

[CONCLUSIONS] The increase in sample sizes during the 1990s may reflect new policies and legislation. Subsequent stability in sample size could be due to modern trial designs (eg, basket/umbrella studies, surrogate endpoints) that require smaller sample sizes. The recent decrease in protocol sample sizes may herald a similar decline for future studies but requires post-market surveillance to verify credibility.

MeSH Terms

Humans; United States; Neoplasms; United States Food and Drug Administration; Drug Approval; Antineoplastic Agents

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