Study casts doubt on benefit of ‘accelerated approval’ cancer drugs

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More than 40% of cancer drugs granted accelerated approval from 2013 to 2017 did not demonstrate clinical benefit in confirmatory trials, according to a study in the Journal of the American Medical Association (JAMA).

The paper ‘Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval’ reviewed 46 drugs granted approval under the US Food and Drug Administration’s (FDA) accelerated approval pathway.

The authors found that from 2013 to 2017, of those drugs with available results, 41% (19/46) did not improve overall survival or quality of life in confirmatory trials after more than five years of follow-up.

The study also showed that among drugs converted to regular approval, 60% of conversions relied on surrogate measures.

The accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered “reasonably likely” to predict clinical benefit. Post-approval clinical trials are then required to confirm whether these drugs offer clinical benefit.

The authors conclude that although accelerated approval can be useful, some cancer drugs do not end up demonstrating benefit in extending patients’ lives or improving their quality of life.

They also add that “patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes”.

Results of the study

The study found that a total of 129 cancer drug–indication pairs were granted accelerated approval from 2013 to 2023. Among 46 indications with more than five years of follow-up (approved 2013-2017), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and seven (15%) remained ongoing after a median of 6.3 years.

Fewer than half (20/46, 43%) demonstrated a clinical benefit in confirmatory trials. Time to withdrawal decreased from 9.9 years to 3.6 years, and time to regular approval increased from 1.6 years to 3.6 years.

Among 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival, 21 (44%) on progression-free survival, five (10%) on response rate plus duration of response, two (4%) on response rate, and one (2%) despite a negative confirmatory trial.

Comparing accelerated and regular approval indications, 18 of 48 (38%) were unchanged, while 30 of 48 (63%) had different indications (e.g., earlier line of therapy).

Diana Spencer, Senior Digital Content Editor, DDW

Reference: Liu ITT, Kesselheim AS, Cliff ERS. Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval. JAMA. Published online April 07, 2024.

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