Treatment with atezolizumab combined with bevacizumab administered first-line in patients with unresectable hepatocelluar carcinoma (HCC) significantly prolonged overall survival (OS) and progression-free survival (PFS) compared to the current standard of care, sorafenib, according to findings presented at the ESMO Asia 2019 Congress (22-24 November, Singapore).

On behalf of colleagues, Prof. Ann Lii-Cheng of the National Taiwan University Cancer Center and National Taiwan University Hospital in Taipei, Taiwan presented findings from the primary analysis of data from the phase 3 IMbrave150 trial (NCT03434379) of atezolizumab plus bevacizumab vs sorafenib in patients with unresectable HCC.

IMbrave150 enrolled patients who had not received prior systemic therapy for HCC. Following 2:1 randomization, 336 patients were treated with atezoliumab at 1200 mg IV plus bevicizumab at 15 mg/kg IV every 3 weeks and 165 patients received sorafenib at 400 mg twice daily. Both treatments were administered until unacceptable toxicity or loss of clinical benefit per investigator. The patients’ baseline demographics were well balanced between treatment arms.

The co-primary endpoints were OS and PFS by independent review facility (IRF)-assessed RECIST v1.1 and key secondary endpoints included IRF-assessed objective response rate (ORR) per RECIST v1.1 and IRF-ORR per HCC modified (m) RECIST v1.1.

The study primary endpoints were met

With median follow-up of 8.6 months, median OS with the atezolizumab combination was not estimable (NE) compared to 13.2 months (95% confidence interval [CI], 10.4, NE) with sorafenib (hazard ratio [HR] 0.58; 95% CI, 0.42-0.79;p = 0.0006). Median PFS with the combination was 6.8 months (95% CI, 5.7-8.3) versus 4.5 (95% CI, 4.0-5.6) with sorafenib (HR 0.59 (95% CI, 0.47-0.76; p < 0.0001).

The response was doubled with atezolizumab plus bevacizumab over sorafenib

The ORR with the respective treatments was 27% vs 12% (p < 0.0001) per IRF RECIST v1.1. According to IRF HCC mRECIST criteria, the response was nearly 3-fold higher with atezolizumab plus bevacizumab compared to sorafenib; the ORR was 33% versus 13% (p < 0.0001), respectively.

According to the investigators, the results were generally consistent across the clinical subgroups evaluated. They also reported that atezolizumab/bevacizumab delayed deterioration of quality of life compared to sorafenib.

The median duration of treatment was 7.4 months with the combination and 2.8 months for sorafenib.

With combined atezolizumab plus bevacizumab, 57% of patients reported grade 3-4 adverse events (AEs) and 55% of patients receiving sorafenib had a grade 3-4 AE. The frequency of grade 5 AEs was also similar at 5% and 6%, respectively.

Conclusions

The combination of atezolizumab plus bevacizumab demonstrated statistically significant and clinically meaningful improvement in both OS and PFS in patients with unresectable HCC who did not receive prior systemic therapy. The safety of the combination was consistent with the known safety profile of each agent, and no new safety signals were identified.

Based on the findings from the IMbrave150 trial, the authors concluded that combined atezolizumab plus bevacizumab has the potential to be a practice changing treatment in the first-line setting for patients with unresectable HCC.