Short FDA Review Time Seen as Bad Sign for Breast Cancer Drug Neratinib

Approval decision set for July 21

Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, has allotted only five hours, or half a day, to the breast cancer drug neratinib (Puma Biotechnology) at an advisory committee meeting scheduled for May 24, according to a report posted on the financial news website The Street. The move is seen as a bad omen for the controversial drug. In the past, Pazdur has used half-day sessions of the FDA’s Oncologic Drugs Advisory Committee (ODAC) to publicly berate flawed cancer treatments.

The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of July 21.

Puma is seeking accelerated approval for neratinib as an extended adjuvant treatment for patients with early-stage human epidermal growth factor receptor 2 (HER2)-overexpressed/amplified breast cancer who have received prior adjuvant trastuzumab (Herceptin)-based therapy. The company’s FDA submission was based largely on data from a phase 3 clinical trial that showed only a modest improvement in invasive disease-free survival (DFS) at the expense of a high rate of severe diarrhea, according to the report. The drug’s risk–benefit profile has caused concern among some observers.

During the past five years, Pazdur has gathered the FDA and its ODAC experts for 12 half-day sessions where cancer drugs were reviewed and voted on. At eight of those sessions––two-thirds of the time––the FDA was sharply critical of the cancer drugs being reviewed, prompting the ODAC panel to vote against approval.

Puma submitted its new drug application for neratinib, an irreversible tyrosine kinase inhibitor, in September 2016. The submission was supported by results from the phase 3 ExteNET study, which showed a two-year DFS rate of 93.9% for the neratinib arm compared with 91.6% for the placebo arm. In a subgroup of subjects with hormone receptor-positive disease, the two-year DFS rates were 95.4% for neratinib and 91.2% for placebo.

Diarrhea was the most common adverse event among neratinib-treated patients, with approximately 39.9% of the patients experiencing grade-3 or higher diarrhea. One patient (0.1%) had grade-4 diarrhea.

The study results were published in February 2016 in Lancet Oncology.

Sources: The Street; April 19, 2017; and Puma Biotechnology; September 20, 2016.

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