New data from the CheckMate 459 study have found that first-line treatment with nivolumab may serve as an effective therapy option for patients with advanced hepatocellular carcinoma (HCC). 

The findings were presented at the ESMO Congress 2019 in Barcelona, Spain on September 27, 2019.

Overall, the study authors found improvements in the overall survival (OS) and response rates and a favorable safety profile in patients with advanced HCC treated with first-line nivolumab. However, the study did not meet its primary endpoint of statistically significant improved OS compared with sorafenib. 

The phase 3 CheckMate 459 study randomized 743 patients with advanced HCC to nivolumab or sorafenib as first-line treatment. The median OS was 16.4 months for nivolumab and 14.7 months for sorafenib (hazard ratio [HR] 0.85; 95% confidence interval [CI]: 0.72-1.02; p=0.0752). This finding did not meet the predefined threshold of statistical significance. However, researchers observed a clinical benefit across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, according to the study.

The results also showed that the overall response rate was 15% for nivolumab, including 14 patients with complete response, and 7% for sorafenib, in which 5 patients who had complete response. Grade 3 and 4 treatment-related adverse were reported in 22% of patients in the nivolumab arm (81 patients) and in 49% of those given sorafenib (179 patients). These led to discontinuation in 4% (16) and 8% (29) patients, respectively.

Although the primary endpoint of OS did not achieve statistical significance in nivolumab versus sorafenib, nivolumab still showed clinically meaningful improvements in OS, overall response rate, and complete response rate a first-line treatment for advanced HCC.

Angela Lamarca, MD, PhD, MSc, of the Christie NHS Foundation Trust, indicated that, despite falling short of meeting its primary endpoint in the trial, nivolumab’s favorable safety profile is still notable.

“The favorable safety profile with nivolumab is of relevance,” Dr Lamarca said in a commentary. “The favorable safety profile becomes apparent in the form of less toxicity-related treatment discontinuation with nivolumab.”

Quality of life is an important factor for some patients when selecting therapy, she added.

Lamarca also noted that the well-designed study had 2 possible limitations, 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.

More research is needed to better understand how to select patients for immunotherapy, Lamarca concluded.

Reference
  1. Clinical benefit trend with first-line immunotherapy in advanced hepatocellular carcinoma [press release]. ESMO Congress website. Published September 27, 2019. https://www.esmo.org/Press-Office/Press-Releases/ESMO-Congress-Hepatocellular-carcinoma-cancer-Checkmate459-Yau. Accessed September 27, 2019.
  2. LBA38_PR Checkmate 459: A randomized, multi-center phase 3 study of nivolumab (nivo) vs sorafenib (sor) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (AHCC). Annals of Oncology. Presented by: Thomas Yau at ESMO 2019 Congress. September 27, 2019. Barcelona, Spain.