Assessment of the Clinical Benefit of Cancer Drugs Receiving Accelerated Approval
Paper cited by one bottleneck page and 15 idea pages, indexed on Europe PMC as PubMed record 31135808 and published in JAMA Internal Medicine; the citing pages link this DOI, which is how the record was matched.
Overview
Importance: The US Food and Drug Administration's (FDA's) accelerated approval pathway allows investigational cancer drugs to be approved by demonstrating a beneficial effect on a surrogate measure (eg, progression-free survival) that is expected to predict a real clinical benefit (eg, overall survival). However, these drugs must undergo postapproval confirmatory studies to evaluate their actual clinical benefits. In an assessment of the accelerated approval pathway published in 2018, the FDA concluded that this pathway was successful because only 5 (5%) of 93 accelerated drug approvals had been withdrawn or revoked over the last 25 years.
Objective: To compare the end points used in preapproval trials leading to accelerated approval with the end points used in the required confirmatory trials that verified clinical benefit and to update the outcomes of accelerated approvals with confirmatory trials that were ongoing at the time of FDA's review.
Design, setting, and participants: A review of the literature on end points used in preapproval and confirmatory trials of cancer drugs that received accelerated approval and a review of the FDA's database of postmarketing requirements and commitments focused on the outcomes of confirmatory trials that were ongoing at the time of FDA's review of cancer drug approvals published in 2018.
Main outcomes and measures: End points used as confirmation of clinical benefit in cancer drugs that received accelerated approval, updated status of the confirmatory trials, and regulatory outcomes for cancer drugs that did not meet expectations in the confirmatory trials.
Results: The FDA published a review of 93 cancer drug indications for which accelerated approval was granted from December 11, 1992, through May 31, 2017. Of these approvals, the FDA reported that clinical benefit was adequately confirmed in 51 and confirmatory trials for 15 of these indications (16% of the main sample) accelerated approvals reported improvement in overall survival. For 19 approvals (37%), the confirmatory trials used surrogate measures that were the same as those used in the preapproval trials. In this updated review, confirmatory trials for 19 of 93 (20%) cancer drug approvals reported an improvement in overall survival, 19 (20%) reported improvement in the same surrogate used in the preapproval trial, and 20 (21%) reported improvement in a different surrogate. Five confirmatory trials were delayed, 10 were pending, and 9 were ongoing. For 3 recent approvals, the primary end points were not met in the confirmatory trials; however, 1 cancer drug indication still received full approval.
Conclusions and relevance: Confirmatory trials for one-fifth (n = 19 of 93) of cancer drug indications approved via the FDA's accelerated approval pathway demonstrated improvements in overall patient survival. Reassessment of the requirements for confirmatory trials may be necessary to obtain more clinically meaningful information.
Indexed on Europe PMC as PubMed record 31135808 (DOI 10.1001/jamainternmed.2019.0462). Matched by DOI alone: one bottleneck page and 15 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.
One bottleneck page and 15 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.
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