Nivolumab shows promise for advanced liver cancer

Nivolumab appeared safe and effective in patients with advanced liver cancer who did not respond to sorafenib, according to results from the CheckMate 040 study presented at the International Liver Congress 2017.

Sorafenib (Nexavar, Bayer) is the only approved systemic therapy to treat patients with advanced liver cancer. However, patients with advanced disease who are intolerant to or have contraindications for sorafenib therapy have limited treatment options.

Nivolumab (Opdivo, Bristol-Myers Squibb), a PD-1 inhibitor, has prolonged survival for multiple malignancies, including kidney cancer, blood cancers, melanoma and non–small cell lung cancer.

The dose–expansion phase of the multicohort, open-label phase 1/phase 2 CheckMate 040 study demonstrated durable responses (median duration of response, 9.9 months; 9-month OS, 74%).

Bruno Sangro , MD, head of the liver unit at Clinica Universidad de Navarra and Liver and Biomedical Research Network in Hepatic and Digestive Diseases in Madrid, and colleagues evaluated the survival, duration of response and safety by etiology with extended follow-up in 145 patients with advanced hepatocellular carcinoma previously treated with sorafenib from that study.

In total, 91% of patients progressed on sorafenib and 8.3% were intolerant. Thirty patients had hepatitis C virus, 43 patients had hepatitis B virus and 72 patients were uninfected.

Objective response rate by blinded independent central review served as the primary endpoint.

Patients received 3 mg/kg nivolumab every 2 weeks.

Median follow-up was 12.9 months.

ORR by blinded independent central review was 14.5% — which included 20% of patients with HCV, 14% with HBV and 12.5% without hepatitis — and 19.3% by investigator assessment. Fifteen of 21 patients (71.4%) had ongoing responses.

Median duration of response was not reached; however, eight patients responded for 12 months or longer. Researchers noted patients responded regardless of tumor cell PD-L1 expression.

Median OS was 16.7 months overall and not reached in the HCV and HBV cohorts. The rate of 12-month OS was 59.9%.

“The reported median survival of 16.7 months in patients previously treated with sorafenib is promising and it encourages the evaluation of nivolumab in patients affected with hepatocellular carcinoma,” Alejandro Forner, MD, member of the European Association for the Study of the Liver governing board, said in a press release.

The safety profile of nivolumab was consistent with that reported in other tumor types.

Grade 3 or grade 4 treatment-related adverse events occurred in 16.6% of patients, including 30% with HCV, 9.3% with HBV and 15.3% of uninfected patients.

Grade 3 to grade 4 aspartate aminotransferase and alanine aminotransferase elevations occurred in 2.1% to 2.8% of patients and were typically reversible.

“The durable responses and survival rates that were achieved with nivolumab are very welcome, especially as the side effects were manageable,” Sangro said in the release. “These data support the potential of nivolumab in the treatment and stabilization of advanced liver cancer in those patients who have progressed on sorafenib, with or without chronic viral hepatitis.” – by Kristie L. Kahl

Reference:

Sangro B, et al. Abstract LBO-003. Presented at: International Liver Congress 2017; April 11-15, 2017; Amsterdam, the Netherlands.

Disclosure: Sangro reports consultant roles with Adaptimmune, AstraZeneca, Bayer Healthcare, Bristol-Meyers Squibb, BTG, Merck and Sirtex; and lecture fees from Bayer Healthcare, Bristol-Myers Squibb and Sirtex. Please see the full study for a list of all other researchers’ relevant financial disclosures.