As reported in The Lancet Oncology by Thomas Yau, MD, and colleagues, the phase III CheckMate 459 trial has shown no improvement in overall survival with first-line nivolumab vs sorafenib in patients with advanced hepatocellular carcinoma.

Study Details

In the open-label trial, 743 patients not eligible for—or with disease progression after—surgery or locoregional treatment from sites in 22 countries were randomly assigned between January 2016 and May 2017 to receive nivolumab at 240 mg every 2 weeks (n = 371) or sorafenib at 400 mg twice daily (n = 372) until disease progression or unacceptable toxicity.

The primary endpoint was overall survival.

Thomas Yau, MD

Overall Survival

At primary analysis, median follow-up was 15.2 months (interquartile range [IQR] = 5.7–28.0 months) in the nivolumab group and 13.4 months (IQR = 5.7–25.9 months) in the sorafenib group. At a minimum follow-up (time from random assignment of the last patient to clinical data cutoff) of 22.8 months, median overall survival was 16.4 months (95% confidence interval [CI] = 13.9–18.4 months) in the nivolumab group vs 14.7 months (95% CI = 11.9–17.2 months) in the sorafenib group (hazard ratio [HR] = 0.85, 95% CI = 0.72–1.02, P = .075). Rates at 12 and 24 months were 60% vs 55% and 37% vs 33%, respectively. No significant differences were observed among the 19% and 81% of patients with tumor PD-L1 expression ≥ 1% and < 1%.    

Median progression-free survival was 3.7 months (95% CI = 3.1–3.9 months) in the nivolumab group vs 3.8 months (95% CI = 3.7–4.5 months) in the sorafenib group (HR = 0.93, 95% CI = 0.79–1.10), with 12- and 24-month rates of 22% vs 14% and 14% vs 6%. Subsequent systemic therapy was received by 38% of the nivolumab group and 46% of the sorafenib group.

Objective response was observed in 15% vs 7% of patients, with complete response in 4% vs 1%. Median duration of response was 23.3 vs 23.4 months. Disease control rates were 55% vs 58%, with median duration of disease control of 7.5 vs 5.7 months.

Adverse Events

Grade ≥ 3 treatment-related adverse events were observed in 22% of patients in the nivolumab group vs 49% of the sorafenib group, the most common being palmar-plantar erythrodysesthesia (< 1% vs 14%), increased aspartate aminotransferase (6% vs 4%), and hypertension (0% vs 7%). Serious treatment-related adverse events were reported in 12% vs 11% of patients, with the most common being colitis (n = 4, 1%) with nivolumab and acute kidney injury (n = 3, < 1%) with sorafenib. Deaths considered related to treatment occurred in four patients in the nivolumab group (due to liver failure in two and hepatotoxicity and subarachnoid hemorrhage in one each) and one patient in the sorafenib group (due to liver failure).

The investigators concluded, “First-line nivolumab treatment did not significantly improve overall survival compared with sorafenib, but clinical activity and a favorable safety profile were observed in patients with advanced hepatocellular carcinoma. Thus, nivolumab might be considered a therapeutic option for patients in whom tyrosine kinase inhibitors and antiangiogenic drugs are contraindicated or have substantial risks.”

Dr. Yau, of the Department of Medicine, University of Hong Kong, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Bristol Myers Squibb in collaboration with Ono Pharmaceutical. For full disclosures of the study authors, visit thelancet.com.