Avastin hearing leads to more uncertainty over drug's future.

I n what could evolve into a major challenge to the U.S. Food and Drug Administration ’ s plans to require improvement in overall survival when confirming the benefit of accelerated-approval cancer-drugs, Genentech plans to conduct a new trial of bevacizumab that will use progression-free survival (PFS) in metastatic breast cancer patients as its primary endpoint, company officials said. The announcement came shortly before a June 27 – 28 hearing, at which a sixmember subpanel of the Oncology Drugs Advisory Committee (ODAC) unanimously rejected the company ’ s appeal of last December ’ s decision to withdraw the drug ’ s provisional approval for breast cancer. Two follow-up trials and data from three other trials presented at the meeting failed to confi rm the level of PFS seen in the original trial that led to accelerated approval. ODAC ’ s decision now goes to FDA Commissioner Margaret Hamburg for a fi nal decision. The company ’ s plans for the new trial, which could take up to 5 years to complete, were revealed near the end of an emotional 2-day hearing that marked the fi rst time a company has challenged an agency decision to withdraw accelerated approval. Other fi rms have voluntarily withdrawn drugs or label indications when follow-up trials failed to confi rm the early evidence of effi cacy, which in cancer drugs usually depended on the surrogate markers such as PFS. Genentech ’ s appeal directly challenges the FDA ’ s efforts to raise standards after giving accelerated approval to new cancer drugs ( see News, J. Natl. Cancer Inst. 2011;103:455 – 7). Many practicing oncologists are also looking for higher standards of fi nal proof because of the escalating cost of new cancer drugs, which for Avastin, can reach $88,000 per year. ODAC earlier this year backed an agency recommendation that drugs granted accelerated approval for common cancers eventually submit at least two confi rmatory trials showing an improvement in overall survival. After that meeting, Richard Pazdur, M.D., director of the oncology drugs division of the Center for Drug Evaluation and Research (CDER), said the agency was leaning toward issuing similar offi cial guidelines for drug developers.