On May 29, 2020, the FDA approved
atezolizumab for use in combination with
bevacizumab, for the treatment of adult patients with unresectable locally advanced or metastatic
hepatocellular carcinoma (HCC) with no prior systemic treatment. The approval was based on data from Study IMbrave150, which randomly allocated (2:1) patients to receive either
atezolizumab plus
bevacizumab (
atezolizumab-
bevacizumab) or
sorafenib. Overall survival (OS) and independently assessed progression-free survival (PFS) in the intent-to-treat population were the primary endpoints. At the time of the primary analysis, the estimated median OS could not be estimated in the
atezolizumab-
bevacizumab arm and was 13.2 months in the
sorafenib arm [HR, 0.58; 95% confidence interval (CI), 0.42-0.79]. The estimated median PFS was 6.8 months (95% CI, 5.8-8.3) and 4.3 months (95% CI, 4.0-5.6) in the
atezolizumab-
bevacizumab and
sorafenib arms, respectively. Adverse reactions occurring in >20% of patients receiving
atezolizumab-
bevacizumab were
hypertension,
fatigue/
asthenia, and
proteinuria. Adverse reactions occurring in >20% of patients receiving
sorafenib were palmar-plantar erythrodysesthesia,
diarrhea,
hypertension, and decreased appetite.
Hemorrhage was reported more frequently in patients receiving
atezolizumab-
bevacizumab (25%) than in patients receiving
sorafenib (17%). An evaluation for the presence of
varices is recommended within 6 months of initiation of
atezolizumab-
bevacizumab in patients with HCC. Approval of
atezolizumab-
bevacizumab is likely to change the treatment paradigm for HCC, given that treatment with
atezolizumab-
bevacizumab resulted in improved OS and PFS compared with
sorafenib, an accepted standard of care for first-line treatment of patients with unresectable HCC.See related commentary by Castet et al., p. 1827.