Nivolumab Shows Benefit in Advanced Hepatocellular Carcinoma

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In patients with advanced hepatocellular carcinoma, treatment with nivolumab (Opdivo) resulted in responses and long-term survival in patients who were either previously treated or naive to sorafenib (Nexavar), CheckMate 040 has shown.1

Nivolumab monotherapy provided early, stable, and durable responses. Efficacy was observed irrespective of hepatitis C or B viral infection status, and responses were durable irrespective of PD-L1 [programmed cell death ligand 1] expression on tumor cells.
— Ignacio Melero, MD

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Altogether 19% of patients responded to the antibody targeting programmed cell death protein 1 (PD-1), with a median duration of response of 17 months in the dose-escalation cohort and not reached in the expansion cohort. At 9 months, more than 70% of patients were alive, reported Ignacio Melero, MD, of Clinca Universidad de Navarra in Pamplona, Spain, who presented the findings from the global phase II trial at the 2017 Gastrointestinal Cancers Symposium.

“Nivolumab monotherapy provided early, stable, and durable responses. Efficacy was observed irrespective of hepatitis C or B viral infection status, and responses were durable irrespective of PD-L1 [programmed cell death ligand 1] expression on tumor cells,” said Dr. Melero.

CheckMate 040 Findings

CheckMate 040 enrolled 262 patients with advanced hepatocellular carcinoma, treating them with nivolumab at 0.1 to 10 mg/kg in the dose-escalation phase (n = 48) and at 3 mg/kg in the dose-expansion phase (n = 214). Previous treatment with sorafenib was allowed (70%), though some patients (30%) were sorafenib-naive. The study included patients with hepatitis C virus infection (25%) or hepatitis B virus infection (25%) as well as patients who were uninfected (50%). Median follow-up was 13.3 months in the dose-escalation phase and 10.5 months in the dose-expansion phase.

By investigator assessment, in the 70% of patients previously treated with sorafenib, the objective response rate was 16.2% in the dose-escalation cohort and 18.6% in the dose-expansion cohort (with complete responses achieved in each group); stable disease was shown in 43.2% and 45.5%, respectively. By blinded independent central review, the response rate was 18.9% and 14.5%, respectively.

Nivolumab in Hepatocellular Carcinoma

  • CheckMate 040 evaluated nivolumab in 262 advanced hepatocellular cancer patients; 70% had received sorafenib, and 30% were sorafenib-naive.
  • The overall response rate was 19% (21.7% in the first-line setting).
  • In the first-line setting, the overall survival rate at 9 months was 77%.
  • Response was similar for viral-infected vs uninfected patients and for high vs low levels of PD-L1 expression.

“Responses were observed irrespective of the expression of PD-1 on tumor cells,” Dr. Melero noted. “PD-L1–positive and –negative patients had similar response rates.”

Responses were durable. In the sorafenib-experienced group, the median duration of response was 17.1 months in the dose-escalation cohort and was not reached in the dose-expansion group.

Median overall survival was 15.0 months and 13.2 months, respectively. The 12-month overall survival rate was 58% in the dose-escalation group and was not available/not calculated in the dose-expansion group (due to premature data). Almost half (46%) the patients were alive 18 months after treatment onset, Dr. Melero reported.

As first-line treatment, the response rate to nivolumab in the dose-expansion cohort was 21.7%, and stable disease was achieved in 43%. The overall survival rate at 9 months was 77%, he reported.

Quality of Life and Toxicity

Patient-reported quality-of-life measures (based on the EQ-5D visual analog scale and EQ-5D index) were stable from baseline until week 25 in both sorafenib-experienced and sorafenib-naive patients in the dose-expansion phase. No clinically meaningful differences were observed between these patient subsets.

“Very few patients were taken off study because of toxicity. The safety profile was manageable and consistent across patient cohorts and was similar to what has been observed in other tumor types. There were no differences in toxicity in the three etiology categories, and no new safety signals were observed,” he said.

The phase III CheckMate 459 study is now evaluating nivolumab in the first-line setting. ■

Disclosure: Dr. Melero has received honoraria from and consulted or advised for AstraZeneca, Bayer, Bristol-Myers Squibb, Incyte, Merck Serono, Merck Sharp & Dohme, and Roche. He also has received institutional research funding from Alligator Bioscience, Pfizer, and Tusk Therapeutics.


1. Melero I, Sangro B, Yau TC, et al: Nivolumab dose escalation and expansion in patients with advanced hepatocellular carcinoma: The CheckMate 040 study. 2017 Gastrointestinal Cancers Symposium. Abstract 226. Presented January 20, 2017.

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