Evaluating the Long-Term Clinical Benefit of Cancer Treatments Granted Accelerated Approval

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History has shown that the FDA generally approves new drugs to the marketplace that are reportedly “shown to be safe and effective” only if the benefits are greater than the risks.¹

Examples date back to the 1980s during the HIV epidemic. At a time when finding a treatment was imperative, the government organization formed an accelerated approval pathway in an effort to help these drugs reach the market quicker based on what it described as promising clinical benefits. However, it’s also important to note that after accelerated approval is granted, manufacturers are then required to conduct post-approval trials in order to confirm that patient benefit and indications should either be withdrawn or converted to regular approval.

Decades later, this form of accelerated approval has gained popularity in the oncology space—nearly one-third of all oncology drug approvals use the pathway, and more than 80% of all accelerated approvals are granted for cancer therapies.¹

A cohort study published in JAMA¹ sought to explore this further, digging deeper into the medications that received accelerated approval from 2013-2017. For those approved drugs that had more than five years of follow-up, the investigators reviewed the timing of confirmatory trial completion, while determining whether confirmatory trials ultimately showed improvement in quality of life or overall survival. For any indications that were converted to regular approval, the confirmatory trial characteristics that stated the conversion decision were reviewed.

In order to expand the amount of available information, publicly available FDA data of accelerated approvals from 2013 to 2023 were used. Results indicated that during this timeframe, 129 cancer drug–indication pairs were given this accelerated approval.

For the 46 indications that had more than five years of follow-up (approved during the 2013 to 2017 timeframe mentioned above), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and seven (15%) were still ongoing after a median of 6.3 years.

Fewer than half (20/46, 43%) displayed a clinical benefit in confirmatory trials. Time to withdrawal dipped from 9.9 years to 3.6 years, while the time to regular approval increased from 1.6 years to 3.6 years. Other results included that:

• Among the 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival
• Twenty-one were converted (44%) on progression-free survival
• Five were converted (10%) on response rate plus duration of response
• Two (4%) were converted on response rate
• One was converted (2%), even with a negative confirmatory trial

There were various study limitations, including that only confirmatory trial data were analyzed to evaluate the clinical benefit of cancer indications for accelerated approvals; it is possible that other trials have the same potential clinical benefit. Also, during the portion of the study that involved a minimum of a five-year follow-up for the clinical benefit cohort, there were still seven drugs awaiting confirmatory trial results, so these could have also proven beneficial.

As a result, the study authors concluded that, “Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within five years of 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.”

Reference

1. Liu ITT, Kesselheim AS, Cliff ERS. Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval. JAMA. Published online April 07, 2024. doi:10.1001/jama.2024.2396