Sponsors seeking accelerated approval for oncology drugs should avoid the temptation of single-arm trials and conduct randomized trials except for indications with a small patient population or where drug activity is high, an FDA advisory panel concluded Feb. 8.

A single-arm trial, which is easier and faster to conduct, should be reserved for rare circumstances, Gary Lyman, Duke University, noted during an Oncologic Drugs Advisory Committee meeting. For Silvana Martino, The Angeles Clinic and Research Institute, that would be when "patients are few and the activity of the drug is considerable."

Modest effects in a single-arm trial are insufficient to justify approval, agreed Malcolm Smith of the National Cancer Institute.

The committee's preference for randomized trials confirms the direction FDA is already moving. Office of Oncology Drug Products Director Richard Pazdur noted that the agency is encouraging sponsors to think randomization before conducting a single-arm trial.

Marginal response rates found in single-arm trials in a refractory setting make it difficult to judge whether they are predictive of clinical benefit, he pointed out.

It's not that a single-arm study will never be acceptable, Pazdur said. But drugs are often submitted with very small response rates and sometimes the true benefit is not known until a randomized trial assesses survival.

Committee members also supported requiring sponsors to conduct two post-approval confirmatory trials, instead of one, and agreed that these trials should be ongoing or at least in the final stages of development at the time of accelerated approval.

FDA sought support for those requirements to ensure that confirmation of accelerated approval can be provided in a timely fashion. If a single trial fails to show efficacy and then a second trial is conducted, it takes too long to determine whether a drug is in fact beneficial, Pazdur said.

-Cathy Dombrowski (c.dombrowski@elsevier.com )

Accelerated And Accompanied: Oncology Drugs Should Use Randomized Trials, FDA Panel Says

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