Immuno-Oncology Resource Center

Immuno-Oncology Resource Center

December 03, 2019
2 min read

Atezolizumab plus bevacizumab extends survival in unresectable HCC

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A combination of atezolizumab and bevacizumab conferred statistically significant and clinically meaningful improvements in PFS and OS compared with sorafenib among patients with unresectable hepatocellular carcinoma, according to results of the randomized phase 3 IMbrave150 study presented at European Society for Medical Oncology Asia Congress.

“This is the first study in 11 years to show an improvement in survival with a new first-line treatment option compared to sorafenib, which had been the standard of care throughout this time,” Ann-Lii Cheng, MD, PhD, director of National Taiwan University Cancer Center, said in a press release. “Atezolizumab plus bevacizumab has the potential to be a practice-changing treatment option in hepatocellular carcinoma.”

Studies have yet to identify a better treatment option for unresectable HCC than sorafenib (Nexavar, Bayer), which has a response rate of about 10% and has been associated with severe adverse events, Cheng added.

However, atezolizumab (Tecentriq, Genentech), a PD-L1 inhibitor, in combination with bevacizumab (Avastin, Genentech), a VEGF inhibitor, appeared safe and showed promising efficacy in a phase 1b study among patients with HCC who had not received prior systemic therapy.

In the phase 3 IMbrave150 study, Cheng and colleagues randomly assigned 501 treatment-naive patients with unresectable HCC in a 2:1 ratio to 1,200 mg IV atezolizumab every 3 weeks with 15 mg/kg IV bevacizumab every 3 weeks (n = 336) or 400 mg sorafenib twice daily (n = 165). Patients continued treatment until unacceptable toxicity or loss of clinical benefit.

PFS and OS, assessed by independent review facility per RECIST version 1.1 criteria, served as primary endpoints. Overall response rate assessed by independent review per RECIST version 1.1 criteria and per HCC modified RECIST (mRECIST) criteria served as key secondary endpoints.

Median follow-up was 8.6 months.

Results showed patients who received atezolizumab plus bevacizumab had significantly longer median PFS than patients who received sorafenib (6.8 months vs. 4.3 months; HR = 0.59; 95% CI, 0.47-0.76). Median OS was not reached in the combination therapy group and was 13.2 months in the sorafenib group (HR = 0.58; 95% CI, 0.42-0.79).

Researchers reported ORRs of 27% with the combination and 12% with sorafenib, according to RECIST 1.1 criteria, and 33% vs. 13%, according to HCC mRECIST criteria (P < .0001 for both).

Median treatment duration was 7.4 months for atezolizumab, 6.9 months for bevacizumab and 2.8 months for sorafenib.


Grade 3 to grade 4 adverse events occurred among 57% of patients in the combination group and 55% in the sorafenib group. Grade 5 adverse events occurred among 5% of the combination group and 6% of the sorafenib group.

Researchers did not identify any new safety signals for atezolizumab or bevacizumab.

“I think this is a breakthrough and, based on the results, the combination of atezolizumab plus bevacizumab could become the new standard of care,” Angela Lamarca, MD, PhD, MSc, consultant medical oncologist at Christie NHS Foundation Trust in the United Kingdom, said in a press release. “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.” – by John DeRosier


Cheng AL, et al. Abstract LBA3. Presented at: European Society for Medical Oncology Asia 2019 Congress; Nov. 22-24, 2019; Singapore.

Disclosures: Cheng reports advisory/consultant roles with Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Exelixis, Merck Serono, Novartis and Roche/Genentech; honoraria from and speakers bureau roles with Eisai, Novartis, Ono Pharmaceutical and Roche/Genentech; and travel expenses from Bayer Yakuhin Ltd. and Merck Serono. Please see the abstract for all other authors’ relevant financial disclosures. Healio could not confirm Lamarca’s relevant financial disclosures at the time of reporting.