Highlights from

ESMO 2019

European Society for Medical Oncology Congress 2019

Barcelona 27 September - 01 October 2019

In hepatocellular carcinoma, CheckMate 459 misses OS endpoint, but some interesting trends emerge

CheckMate 459 in patients with advanced hepatocellular carcinoma (HCC) did not meet its prespecified primary endpoint for improved overall survival (OS), despite showing a trend towards clinically meaningful improvements in survival and response rates and a favourable safety profile with first-line immunotherapy agent nivolumab compared with current standard treatment, sorafenib [1].

The data, reported by Dr Thomas Yau (University of Hong Kong, China) originated from the phase 3 CheckMate 459 study, which randomised 743 patients with advanced HCC to receive nivolumab every 2 weeks or oral sorafenib twice daily as first-line treatment. Median OS was 16.4 months for nivolumab and 14.7 months for sorafenib (HR 0.85; 95% CI 0.72-1.02; P=0.0752; see Table). This did not meet the predefined threshold of statistical significance. However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread. The overall response rate was 15% for nivolumab (including 14 patients with complete response) and 7% for sorafenib (5 patients with complete response). Grade 3/4 treatment-related adverse events were reported in 22% of patients in the nivolumab arm (81 patients) and in 49% of those given sorafenib (179 patients). Adverse events led to discontinuation in 4% (n=16) and 8% (n=29) of the patients, respectively.

Dr Yau said, “the primary analysis demonstrated a non-significant trend towards clinically meaningful OS benefit. Importantly, there was also a higher complete response rate with nivolumab compared with sorafenib.” He added that the patient-reported findings suggested that patients in the nivolumab arm experienced better quality of life and further supported clinical data that demonstrated a treatment benefit for nivolumab vs sorafenib in advanced HCC. Invited discussant Dr Arndt Vogel (Hannover Medical School, Germany) noted that regorafenib, lenvatinib, cabozantinib, and ramucirumab are other tyrosine kinase inhibitors in the second-line setting of advanced HCC that may account for some of the results.

Two possible limitations were mentioned, namely the unselected population and the predefined threshold of statistical significance. Results suggested patients with high PD-L1 had an increased response rate only in the nivolumab arm suggesting its potential role as a predictor biomarker, but preselection of patients based on PD-L1 will require another study.

Keywords: CheckMate 459; Carcinoma, Hepatocellular; B7-H1 Antigen; Immunotherapy; Nivolumab

Table. Results from 743 patients with advanced HCC were randomised to nivolumab (NIVO; n=371) or sorafenib (SOR; n=372) with minimum follow-up of 22.8 months at data cut-off.

Table. Results from 743 patients with advanced HCC

OS, overall survival; PFS, progression-free survival; ORR, overall response rate.

  1. Yau T et al. ESMO Congress 2019. Abstract LBA38_PR.


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