Liver Cancer Monotherapy Indication for Nivolumab Withdrawn

Sharon Worcester

July 27, 2021

The indication for nivolumab (Opdivo) as monotherapy for hepatocellular carcinoma (HCC) for patients previously treated with sorafenib has been voluntarily withdrawn by the manufacturer, Bristol-Myers Squibb (BMS). The company said it made the "difficult decision" after consultation with the US Food and Drug Administration (FDA).

No other indications for nivolumab are affected. The immunotherapy checkpoint inhibitor is approved for use in many other cancer types, including melanoma and lung cancer.

It also continues to be approved for use in HCC in combination with ipilimumab (Yervoy) for patients who experience disease progression with or cannot tolerate sorafenib,

The liver cancer monotherapy indication was granted an accelerated approval by the FDA in 2017 on the basis of data from the phase 1/2 CheckMate-040 trial, which showed tumor responses in some patients who received nivolumab.

However, the confirmatory CheckMate-459 trial, which compared nivolumab and sorafenib (Nexavar) in the frontline setting, failed to show a statistically significant benefit in overall survival (OS) with nivolumab.

In April 2020, a meeting of the FDA Oncology Drug Advisory Committee (ODAC) considered this and five other "dangling" accelerated approvals of immunotherapy for various cancer types.

That ODAC panel voted 5-4 against maintaining the liver cancer monotherapy indication for nivolumab.

As reported by Medscape Medical News, the FDA had requested feedback from ODAC on the indication in light of new findings regarding another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), which was granted full approval on the basis of OS benefit demonstrated in the IMbrave150 trial.

The split vote by the ODAC panel underscores the challenges the FDA faces in granting accelerated approvals. At the time of the vote, ODAC panelist Philip C. Hoffman, MD, of the University of Chicago, supported keeping the indication, noting an "unmet need for second-line immunotherapy," whereas ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, Utah, said his "no" vote reflected his doubts that BMS would produce data to support the indication in a timely manner.

"We are disappointed by the position the advisory committee and the FDA have taken regarding the continued approval of Opdivo monotherapy as a treatment for HCC [after] sorafenib," Jonathan Cheng, senior vice president and head of oncology development for BMS, said in a company-issued statement.

"HCC is a complex and challenging disease and, for patients who are initially treated with sorafenib and either cannot tolerate treatment or whose disease progresses, immunotherapy is an important treatment option," he commented. He noted that nivolumab was the most commonly used treatment in the post-sorafenib setting.

Sharon Worcester is an award-winning medical journalist at MDedge News, part of the Medscape Professional Network.

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