At a minimum follow-up of 33.6 months, nivolumab as a first-line treatment for advanced hepatocellular carcinoma did not show statistically longer overall survival (OS) over monotherapy with sorafenib. Nivolumab had a more favourable and manageable safety profile and greater preservation of liver function over time compared with sorafenib, according to Dr Bruno Sangro of the Clinica Universidad de Navarra and CIBEREHD in Pamplona, Spain and colleagues who presented the long-term findings from the CheckMate 459 study at ESMO World Congress on Gastrointestinal Cancer 2020 Virtual (1-4 July).
The study team wrote in the background that patients with advanced hepatocellular carcinoma who are not amenable to surgical resection or locoregional therapy may be treated with multitargeted kinase inhibitors or immune checkpoint inhibitor-based combination therapy.
Sorafenib is approved as first-line treatment in that setting. However, it provides only a modest survival benefit. Despite currently approved first-line treatments for advanced hepatocellular carcinoma, prolonging survival while improving treatment tolerability remains an unmet medical need.
The CheckMate 459 study (NCT02576509) is a phase III trial that compared first-line treatment with nivolumab vs sorafenib in patients with advanced hepatocellular carcinoma. Initial efficacy and safety data were previously presented by Yau et al. at ESMO 2019 Congress in Barcelona who reported that the protocol-defined statistical significance threshold for OS was not met, although nivolumab showed clinical benefit.
At ESMO World Congress on Gastrointestinal Cancer 2020 Virtual, the study team presented long-term follow-up results. In CheckMate 459, 743 systemic therapy-naive patients at least 18 years old with advanced hepatocellular carcinoma and Child-Pugh A liver function were randomised 1:1 to nivolumab (n = 371) or sorafenib (n = 372). The study primary endpoint was OS. Secondary endpoints were objective response rate and progression-free survival by blinded independent central review per RECIST v1.1, efficacy by PD-L1 tumour cell expression, and safety.
The authors reported that with a minimum follow-up of 33.6 months, nivolumab demonstrated longer median OS of 16.4 months (95% confidence interval [CI] 14.0-18.5) vs 14.8 months with sorafenib (95% CI 12.1-17.3), hazard ratio (HR) 0.85 (95% CI 0.72-1.00); nominal p value = 0.0522. The 33-month OS rates for nivolumab and sorafenib were 29% (95% CI 25-34) and 21% (95% CI 17-25), respectively.
Futhermore, the authors reported that a consistent benefit was observed with nivolumab regardless of baseline PD-L1 expression (PD-L1 ≥1% HR 0.80, 95% CI 0.54-1.17; PD-L1 <1% HR 0.84, 95% CI 0.70-1.01). Median OS in patients with PD-L1 ≥1% was longer with nivolumab vs sorafenib, 16.1 months (95% CI 8.4-22.3) vs 8.6 months (95% CI 5.7-16.3), respectively.
Among patients with hepatitis C virus (HCV) and hepatitis B virus (HBV) aetiology, median OS was numerically longer with nivolumab versus sorafenib, 17.5 vs 12.7 months (HR 0.72, 95% CI 0.51-1.02) for HCV and 16.1 vs 10.4 months (HR 0.79, 95% CI 0.59-1.07) for HBV, respectively.
Nivolumab demonstrated greater liver function preservation over time than sorafenib as evidenced by albumin-bilirubin levels and Child-Pugh scores.
Seven patients (2%) in the nivolumab arm and 77 patients (21%) in the sorafenib arm received subsequent therapy with immune checkpoint inhibitor.
Nivolumab demonstrated a more favourable safety profile compared with sorafenib, with grade 3-4 treatment-related adverse events occurring in 82 patients (22.3%) and 180 patients (49.6%), respectively.
The authors concluded that a long-term follow-up data of CheckMate 459 study show for 1,5 months longer OS with first-line nivolumab than with sorafenib in the management of advanced hepatocellular carcinoma, but this difference was not statistically significant. Nivolumab had a more favourable and manageable safety profile and greater preservation of liver function over time compared with sorafenib, which is consistent with previous reports. There were no new or unexpected safety signals observed.
The study was funded by Bristol Myers Squibb (Princeton, NJ, USA).
LBA3 - Sangro B, Park J, Finn R, et al. CheckMate 459: Long-term (minimum follow-up 33.6 months) survival outcomes with nivolumab versus sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma. ESMO World Congress on Gastrointestinal Cancer 2020 Virtual (1-4 July).