- Though the overall survival (OS) endpoint in the CheckMate-459 trial did not achieve statistical significance, improved QoL and reduced treatment burden were observed for patients treated with nivolumab compared with sorafenib.
Why this matters
- Few effective treatment options are available for patients with advanced hepatocellular carcinoma (aHCC) whose tumors are not eligible for surgical resection or local therapy.
- Immuno(mono)therapy is a promising approach, but new biomarkers are needed to identify patients who truly benefit from the therapy.
- Sorafenib is approved as first-line therapy for aHCC, but there is still an unmet need to prolong survival and increase tolerability.
- Nivolumab demonstrated durable responses, safety, and promising long-term survival in CheckMate 040.
- Phase 3 study to compare clinical efficacy and safety of nivolumab vs sorafenib as first-line therapy in patients with aHCC.
- Systemic therapy-naive patients aged ≥18 years with aHCC randomised 1:1 to nivolumab (743 patients, 240 mg IV Q2W) or sorafenib (372 patients, 400 mg oral bid), with minimum follow-up of 22.8 months.
- Primary endpoint: OS.
- Additional endpoints were objective response rate (ORR) and progression-free survival (PFS), efficacy by tumour programmed-death ligand 1 (PD-L1) expression, and safety.
- Funding: Bristol-Myers Squibb.
- OS did not meet the predefined threshold of statistical significance (HR 0.84, P=0.0419).
- Median OS was 16.4 months for nivolumab and 14.7 months for sorafenib (HR 0.85; P=0.0752).
- Clinical benefit was observed across predefined subgroups, including hepatitis infection status, presence of vascular invasion and/or extrahepatic spread, and region (Asia vs non-Asia).
- ORR was 15% for nivolumab and 7% for sorafenib (14 vs 5 patients with complete response).
- Grade 3/4 treatment-related adverse events were reported in 22% with nivolumab and 49% with sorafenib and led to discontinuation in 4% and 8%, respectively.
- “Formally it’s another negative phase-III immunotherapy study, but there are clinically meaningful data on efficacy, safety and QoL in favor of nivolumab. mOS has increased in first-line HCC, and the quality and quantity of subsequent therapies have improved. Now we need biomarkers to identify patients that benefit from immuno(mono)therapy,” said Per Pfeiffer, Odense University Hospital, who was not involved in the study.