FDA Aims to Broaden Access to New Therapies

The FDA is ramping up its accelerated approval pathway to make new drugs more accessible to patients with cancer earlier in the course of their disease. Project FrontRunner, an initiative of the FDA's Oncology Center of Excellence, urges drugmakers to develop and seek approval of experimental drugs as first-line treatments for patients with advanced or metastatic disease, rather than focusing on patients who have had multiple therapies and/or exhausted available options.

“Despite increasing novel approvals of cancer drugs over the past decade or so, the approach to developing drugs has not really changed over the past 50 years,” says FDA program lead Lola Fashoyin-Aje, MD, MPH. “Most initial approvals are still occurring in the multiple refractory setting, and the evidence brought forth to support approvals has still largely been derived from small, single-arm trials in very advanced metastatic settings using the [accelerated approval] pathway.”

Project FrontRunner enhances accelerated approval and addresses certain problematic issues, including overreliance on single-arm trials and delayed initiation of postmarket confirmatory trials—which may occur well after accelerated approval has been granted, according to Fashoyin-Aje.

“There seems to be a misconception that [accelerated approval] is only for drugs that fill an unmet medical need in later lines of treatment,” she says. “While it's critical to ensure that there are treatment options for patients at all stages of disease, one thing that may not be as carefully thought through is where a given drug may have the biggest impact on outcomes—in earlier settings where a new drug can meaningfully increase survival and potentially improve the quality of that survival if it replaces a less effective and often more toxic therapy.”

Besides expanding access, the program is likely to improve the overall benefit–risk assessment of candidate drugs, says Craig Tendler, MD, of Janssen Research & Development, part of Johnson & Johnson, based in Raritan, NJ.

“With Project FrontRunner, trials can be running in parallel in the relapsed or refractory setting and in the first-line treatment setting,” says Tendler. “That gives us a second shot on goal to pursue accelerated approval not only in a heavily pretreated population, but also in an earlier disease setting where typically we see an enhanced benefit as compared to waiting until patients have gone through several therapies and their disease has progressed or relapsed multiple times.”

Potentially effective drugs can be overlooked if tested only after other options have failed, notes George Demetri, MD, of Dana-Farber Cancer Institute in Boston, MA.

“We know cancer has an unstable genome and likely evolves, so that by the time you get to three or four lines of therapy, you're not even treating the same disease—and it's probably worse,” he explains. “We might have a terrific drug that's potentially very effective as first-line therapy but shows only marginal or even negative benefits in a second or later line.”

Project FrontRunner also opens up the possibility of discovering potentially curative treatments for some cancers, Demetri says.

“Many advanced metastatic breast, colorectal, and other cancers have existing treatment options with proven survival benefits, but we know we are not curing most of these patients,” he notes. “We need to find ways to test new drugs earlier while at the same time ensuring that patients don't miss out on the benefits of currently approved therapies.” —Janet Colwell