Most Cancer Drugs With Accelerated Approval Don’t Show Benefit


Researchers were unable to find a significant benefit for patients for the majority of cancer medications given accelerated FDA approval.

Among 46 oncology drugs given accelerated FDA approval with at least 5 years of follow-up, only 20 (43%) showed a clinical benefit for patients’ overall survival or improvement of quality of life.1

The accelerated approval pathway was developed in response to the HIV epidemic to get promising drugs that filled an unmet need to the market sooner. Drugs that receive an accelerated approval still need to confirm their benefit through mandatory post approval trials in order to gain full, traditional approval.1

Although accelerated approval originated to assist treatment in HIV patients, it is most commonly used for oncology drugs with 80% of all accelerated approvals involving cancer therapies and a third of all cancer medications receiving the accelerated approval pathway.1

To test the clinical benefits of these medications, researchers analyzed 129 cancer therapies given accelerated approval between 2013 and 2023. They then observed outcomes of the 46 indications with more than 5 years of patient follow-up.

FDA Approval Pathways

Of the 46 indications with accelerated FDA approval and a 5-year follow-up, 29 (63%) were converted to regular approval after confirmatory trials. Ten (22%) indications were withdrawn and 7 (15%) remained without a definitive outcome.1

From 2013 to 2017, the time from accelerated approval to the projected completion of a confirmatory trial, made at the time of approval, increased 1.1 years. Of the 29 drugs converted to regular approval, the duration of conversion was 1.6 years in 2013 and 3.6 years in 2017. For the 10 indications withdrawn from their confirmatory trials, the duration from accelerated approval to withdrawal decreased from 9.9 years to 3.6 in 2017.1

As a whole, “the time between projected trial completion to actual withdrawal or conversion [to regular approval] narrowed over time,” wrote the authors.

The most recent example of an approval being withdrawn is melphalan flufenamide (Pepaxto, Melflufen), which had its approval withdrawn on February 23, 2024.2 It had received accelerated approval 3 years earlier in February 2021 for use in combination with dexamethasone to treat patients with relapsed/refractory multiple myeloma who had received at least 4 prior lines of therapy.

Primary Outcomes of Cancer Therapies Given Accelerated Approval

Determining primary outcomes as improvement of quality of life and overall patient survival rates, researchers found that 26 (57%) of the 46 indications with at least 5 years of follow-up data did not improve either.1

Further assessing outcomes in drugs that received regular approvals after confirmatory trials, only 7 of 29 indications (24%) improved both overall survival and quality of life. Another 7 indications (24%) improved overall survival but not quality of life, while 6 (21%) improved quality of life but not overall survival. Finally, there were 9 indications that received regular approval without showing benefits for either outcome.1

Outside of drug indications with a 5-year follow-up data, researchers analyzed 66 indications with accelerated approval that were either given regular approval or withdrawn after completion of confirmatory trials. Of the 66 indications, 48 (73%) were converted to regular approval and 18 (27%) were withdrawn.

Among the 48 indications converted, 19 (40%) were converted based on overall survival; 21 (44%) based on improvement in progression-free, event-free, or disease-free survival; 5 (10%) based on response rate plus duration of response; 2 (4%) based on response rate; and 1 (2%) was converted despite a negative confirmatory trial that showed no improvement in either primary outcome.1

“Among this cohort of accelerated approvals for cancer drugs, some improved overall survival, several ineffective drugs were withdrawn, multiple drugs had ongoing confirmatory studies, and others were converted to regular approval based on surrogate measures,” wrote the authors.1

With sporadic outcomes for cancer drugs with accelerated approval, researchers concluded that patients should exercise due diligence before accepting prescriptions for drugs with accelerated approval.

“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,” concluded the authors.1


1. Liu ITT, Kesselheim AS, Cliff ERS. Clinical benefit and regulatory outcomes of cancer drugs receiving accelerated approval. JAMA. April 07, 2024. doi:10.1001/jama.2024.2396

2. Seymour C. FDA confirms decision to withdraw melphalan flufenamide approval in multiple myeloma. OncLive®. February 23, 2024. Accessed April 17, 2024.

This story first appeared on Drug Topics.

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