Combination therapy with the programmed cell death ligand 1 inhibitor atezolizumab and the VEGF inhibitor bevacizumab significantly improved overall and progression-free survival in patients with unresectable hepatocellular carcinoma (HCC) compared to sorafenib, according to findings from the phase III IMbrave150 trial presented by Cheng et al at the European Society for Medical Oncology (ESMO) Asia Congress 2019 (LBA3).

“This is the first study in 11 years to show an improvement in survival with a new fist-line treatment option compared to sorafenib, which has been the standard of care throughout this time,” said first study author Ann-Lii Cheng, MD, PhD, Director of the National Taiwan University Cancer Center. He added, “Atezolizumab plus bevacizumab has the potential to be a practice-changing treatment option in HCC. Despite many studies over the past 11 years, we have been unable to find any better treatment option. This has been very frustrating because sorafenib has a response rate of around 10% and is associated with severe side effects.”

IMbrave150

The phase III IMbrave150 study randomized 501 patients with unresectable HCC on a 2:1 basis to atezolizumab (1,200 mg intravenously every 3 weeks) plus bevacizumab (15 mg/kg intravenously every 3 weeks) or sorafenib (400 mg twice daily). The patients continued with their assigned treatment until unacceptable toxicity or loss of clinical benefit as judged by study investigators.

Results showed the hazard ratio (HR) for overall survival (OS) was 0.58 (95% confidence interval = 0.42–0.79, P = .0006) after a median follow-up of 8.6 months. The median OS has not yet been reached for atezolizumab plus bevacizumab, compared to 13.2 months for patients treated with sorafenib. Median progression-free survival (PFS) was also significantly increased (median 6.8 vs 4.3 months, HR = 0.59; 95% CI = 0.47–0.76, P < .0001).

Overall response rate was 27% with atezolizumab plus bevacizumab vs 12% compared to sorafenib (P < .0001) based on independent assessment using RECIST 1.1 criteria, and similarly increased using HCC mRECIST criteria (33% vs 13%, P < .0001). Atezolizumab plus bevacizumab delayed deterioration in quality of life compared to sorafenib.

Grade 3–4 adverse events occurred in 57% of patients treated with atezolizumab plus bevacizumab and 55% of those receiving sorafenib. Grade 5 adverse events occurred in 5% and 6% of patients, respectively.

Commentary

Angela Lamarca, MD, PhD

Angela Lamarca, MD, PhD, Consultant Medical Oncologist at the Christie NHS Foundation Trust, commented, “I think this is a breakthrough and based on the results, the combination of atezolizumab plus bevacizumab could become the new standard of care. The results are clinically meaningful in the setting of advanced HCC, as well as statistically significant. The delayed deterioration in quality of life is also important—patients are living longer and their quality of life is better.”

She considered the study was well-designed with several strengths, including its large sample size, the use of a combination endpoint of PFS and OS, assessment of response/progression by a central reviewer, and analysis based on the intention-to-treat population.

Dr. Lamarca also noted that the median follow-up of 8.6 months is relatively short, with the median OS for atezolizumab plus bevacizumab not yet being reached.

Disclosure: For full disclosures of the study authors, visit academic.oup.com.