Single-Agent Nivolumab Withdrawn for Hepatocellular Carcinoma Treatment

Hepatocellular carcinoma.

In consultation with the FDA, Bristol Myers Squibb has voluntarily withdrawn nivolumab (Opdivo®) as a single-agent treatment for patients with hepatocellular carcinoma (HCC) who had previously been treated with sorafenib.

Nivolumab had previously been granted accelerated approval from the FDA in 2017, which was based on the phase 1/2 CheckMate 040 clinical trial (NCT01658878). The withdrawal of this treatment is due to the lack of statistical significance in the final overall survival results of CheckMate 459, which was intended to confirm nivolumab’s efficacy in the treatment of HCC.

“The primary end point of overall survival did not achieve statistical significance versus sorafenib,” wrote Thomas Yau, MBBS, MRCP, FHKCP, FHKAM, Clinical Associate Professor at The University of Hong Kong’s Department of Medicine, and colleagues, in their published October 2019 abstract in the Annals of Oncology (NCT02576509), on which the withdrawal was based.

This phase 3 study enrolled 743 systemic therapy–naive patients with HCC who were randomized 1:1 to either 240 mg nivolumab intravenously every two weeks or to 400 mg sorafenib orally twice a day. The primary end point was overall survival. Secondary end points were objective response rate, progression-free survival, and safety.

The median overall survival was 16.4 months in the nivolumab arm compared with 14.7 months in the sorafenib arm, a difference which was not statistically significant. The overall response rate in the nivolumab group was 15%, while the sorafenib group had an overall response rate of 7%. In the nivolumab group, grade 3/4 adverse events were reported in 22% of patients, while 49% of patients in the sorafenib group experienced grade 3/4 adverse events.

In a press release, Bristol Myers Squibb wrote that nivolumab as a single agent and also in combination with ipilimumab (Yervoy®) is being tested in additional trials and in different disease settings, with the intent of pursuing new therapeutic approaches for patients with HCC.

For More Information

Yau T, Park JW, Finn RS, et al (2019). CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Ann Oncol, 30(suppl_5):v874-v875. Abstract LBA38_PR. DOI:10.1093/annonc/mdz394.029

Yau T, Kang YK, Kim TY, et al (2020). Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the CheckMate 040 randomized clinical trial. JAMA Oncol, 6(11):e204564. DOI:10.1001/jamaoncol.2020.4564 (2021). An investigational immuno-therapy study of nivolumab compared to sorafenib as a first treatment in patients with advanced hepatocellular carcinoma. NLM identifier: NCT02576509. (2021). An immuno-therapy study to evaluate the effectiveness, safety and tolerability of nivolumab or nivolumab in combination with other agents in patients with advanced liver cancer (CheckMate040). NLM identifier: NCT01658878.

Bristol Myers Squibb (2021). Bristol Myers Squibb statement on Opdivo® (nivolumab) monotherapy post-sorafenib hepatocellular carcinoma U.S. indication. Available at:

Image credit: Nephron. Licensed under CC BY-SA 3.0

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