Bristol Myers' Opdivo Fails to Maintain Accelerated Approval in Liver Cancer


The U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee did not agree in a recent meeting to maintain the accelerated approval of Bristol Myers Squibb’s Opdivo (nivolumab) as a second-line treatment of hepatocellular carcinoma. Five Committee members voted against the accelerated approval, while four voted to maintain the approval.

“Immunotherapy is an important next treatment option for patients who have progressed on sorafenib or were unable to tolerate it,” said Bristol Myers Squibb’s development lead of gastrointestinal cancers, Ian M. Waxman, M.D., in a statement. “We are disappointed with today’s outcome for patients, and we will work closely with the FDA as it completes its review. Immunotherapies have changed the way we treat many forms of advanced cancer. We’re proud of the role Opdivo has played in helping to evolve the HCC treatment landscape, and we remain focused on delivering innovative therapies for HCC patients in need.”

In 2017, Bristol Myers Squibb’s monoclonal antibody was granted accelerated approval in liver cancer based on findings from the Phase I/II CheckMate-040 trial. But the confirmatory, randomized CheckMate-459 trial of first-line Opdivo versus sorafenib in patients with advanced hepatocellular carcinoma two years later failed to meet its primary endpoint of overall survival.

Opdivo is being proposed for other indications besides hepatocellular carcinoma. Yesterday, the FDA accepted priority review of Bristol Myers Squibb's application for Opdivo as an adjuvant therapy in patients with muscle-invasive urothelial carcinoma. The application is supported on by a data from the pivotal Phase III CheckMate-274 trial, which showed Opdivo almost doubled the disease-free survival rate in patients with high-risk invasive urothelial carcinoma compared with placebo.

“After patients undergo surgery for muscle-invasive urothelial carcinoma, they continue to face uncertainties given the high rate of disease recurrence and the lack of safe and effective treatment options,” according to a statement made by Dana Walker, M.D., M.S.C.E., Bristol Myers Squibb’s vice president and development program lead of genitourinary cancers. “Based on the ground-breaking disease-free survival results from CheckMate-274, we believe Opdivo has the potential to change the future of treatment for muscle-invasive urothelial carcinoma. We look forward to working with the FDA towards the goal of bringing the first adjuvant immunotherapy option to these patients in the U.S.”

CheckMate-274 is only one out of four Phase III trials that have demonstrated benefit with Opdivo in early stage cancers, including melanoma (CheckMate-238), esophageal/gastroesophageal junction cancer (CheckMate-577) and non-small cell lung cancer (CheckMate-816).

Earlier this month, the FDA approved Opdivo, in combination with chemotherapy, as the first immunotherapy for the initial treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma. Approval was based on positive data from the Phase III CheckMate 649 trial, which showed that treatment with the agent reduced the risk of mortality by up to 20%.

“Today’s approval is the first treatment in more than a decade to show a survival benefit for patients with advanced or metastatic gastric cancer who are being treated for the first time,” according to a statement made by Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “The FDA is committed to bringing new safe and effective treatment options like Opdivo to patients with advanced cancer.”

During the same meeting that voted against maintaining Opdivo’s second-line liver cancer indication, the FDA's Oncologic Drugs Advisory Committee voted five-to-three in favor of maintaining the accelerated approval for Merck's Keytruda (pembrolizumab) as a first-line treatment for carboplatin-resistant urothelial carcinoma. The FDA panel also voted to maintain the accelerated approval of the drug for the indication of hepatocellular carcinoma, but the members didn't reach the majority on a vote to maintain the biologic agent’s third-line indication for stomach cancer. Roche's Tecentriq (atezolizumab) also won the Committee members’ support do too positive survival data from a confirmatory trial.

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