What You Need to Know About the FDA's Approval of Opdivo-Yervoy for Hepatocellular Carcinoma

The Food and Drug Administration (FDA) recently approved the combination use of Opdivo (nivolumab) and Yervoy (ipilimumab) for the treatment of patients with advanced hepatocellular carcinoma (HCC) who were previously treated with Nexavar (sorafenib).

This is the only dual immunotherapy approved by the FDA in this setting of patients with HCC and was based on the results of the phase 1/2 CheckMate-040 trial. The overall trial was to look at Opdivo in patients with advanced HCC, with the Opdivo and Yervoy cohort showing a duration of responses that lasted from 4.6 to 30.5 months with 88% of responses lasting at least 6 months, 56% at least 12 months and 31% at least 24 months, according to a Bristol Myers Squibb spokesperson.

“HCC is an aggressive disease in need of different treatment approaches,” Dr. Anthony B. El-Khoueiry, lead investigator and phase 1 program director at the Keck School of Medicine, University of Southern California (USC) and the USC Norris Comprehensive Cancer Center, said in the original press release regarding the approval. As the incidence of liver cancer rises in the United States, HCC has become the most common and aggressive from of the disease with relapsed patients in need of new treatments after the first line of treatment fails. This is why the FDA granted accelerated approval to the Opdivo and Yervoy combination for this patient group previously treated with Nexavar, a chemotherapy for liver cancers.

The CheckMate-040 trial is a phase 1/2, dose-escalation/dose expansion, open-label study of Opdivo in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis C or B. Researchers envaulted the Opdivo-Yervoy combination in 49 patients with advanced HCC, 33% of these patients responded to this treatment with 8% demonstrating a complete response and 24% exhibiting a partial response after a minimal follow up of 28 months. Overall response was reported in 35% of patients.

According to a Bristol Myers Squibb spokesperson, the Opdivo-Yervoy combination acts on the CTLA-4 and PD-1 immune checkpoints that while beneficial alone there is evidence that the mechanisms can work together to produce a greater effect in patients. In the case of Yervoy, it may help the patient’s immune system to activate more T cells that help fight cancer cells while Opdivo assists in already active T cells discovering cancer cells. The researchers believe the combination can work to discover and then deploy newly activated T cells in the fight against cancer.

However, according to a Bristol Myers spokesperson, this combination therapy can cause the immune system to attack normal organs and tissues which can lead to serious complications and may happen more often on this combination therapy.

In the CheckMate-040 trial serious side effects were seen in 59% of patients on the treatment, including pyrexia, diarrhea, anemia, increased aspartate aminotransferase, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin and pneumonitis in more than 4% of patients. The most common of these side effects was rash, pruritus, musculoskeletal pain, diarrhea, cough, decreased appetite, fatigue, pyrexia, abdominal pain, headache, nausea, dizziness, hypothyroidism and weight decrease reported in more than 20% of patients.

The approval for the Opdivo-Yervoy combination was granted on March 10^th, 2020.

Read CURE’s original coverage of the approval.