CheckMate-040: Opdivo may present an option for Child-Pugh B HCC

SAN FRANCISCO — Patients with advanced hepatocellular carcinoma with Child-Pugh B status experienced encouraging efficacy and safety outcomes after treatment with PD-1 inhibitor Opdivo, according to data presented at The Liver Meeting 2018.

Masatoshi Kudo, MD, of Kinki University in Osaka, Japan, suggested that many patients with HCC with Child-Pugh B liver function status have a poorer prognosis than those with Child-Pugh A status. “But they are often excluded from advanced HCC trials,” he said. Because data are lacking, there is a “high unmet need” for therapeutic options in this patient population, according to Kudo.

In the current study, Kudo and colleagues conducted the first prospective trial investigating Opdivo (nivolumab, Bristol-Myers Squibb) in patients with advanced HCC with Child-Pugh B status. The 49 eligible participants were naive to Nexavar (sorafenib, Bayer). They underwent treatment with a 240-mg flat IV dose of nivolumab for 30 minutes every 2 weeks.

Overall response rate (ORR) based on investigator assessment served as the primary endpoint, while secondary endpoints included disease control rate, duration of response, time to response, time to progression, progression-free survival and overall survival. “Safety was also analyzed,” Kudo said.

Median follow-up duration was 11.8 months.

Baseline disease characteristics showed that around three-quarters of the cohort was Child-Pugh B7, and just over 20% were Child-Pugh B8. “Extrahepatic metastases were lower in the Child-Pugh B patients compared with Child-Pugh A patients,” Kudo said.

Results showed an ORR of 10% and a disease control rate by investigator assessment of 55%.

The median time to response was 2.7 months (range, 1.2–4.2), while the median duration of response was 9.9 months (range, 2.8-9.9). “Deep responses were observed in some responders irrespective of etiology,” Kudo said. Regarding tumor burden change, Kudo added that responders showed a durable response. “It was much longer than historical patients with Child-Pugh B status treated with sorafenib.”

The median OS was 7.6 months (95% CI, 4.4–10.5), which Kudo noted was also longer than historical comparators.

Safety data showed that any grade events occurred in just over half of the cohort, while grade 3 to 4 events occurred in about one-quarter (24.5%).

Hepatobiliary disorders were the most commonly reported grade 3-4 events, at 6.1%. Only 2 patients, or 4.1%, discontinued treatment due to study drug toxicity, which was comparable to the rate observed in Child-Pugh A patients, according to Kudo. He noted that the safety profile of nivolumab in patients with Child-Pugh B status is comparable to patients with Child-Pugh A status.

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“Hepatic select treatment-related adverse events were seen within the first few months of treatment,” he said, and noted a hepatitis immune-related event. “The time to onset for the hepatitis immune-mediated event was 3.9 weeks.”

“Nivolumab showed promising efficacy and tolerability in patients with Child-Pugh B status, supporting further investigation in this patient population,” he concluded. – by Rob Volansky

Reference:

Kudo M, et al. Abstract LB-2. Presented at: The Liver Meeting 2018; Nov. 9-13, 2018; San Francisco.

Disclosure: Kudo reports no relevant financial disclosures.