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For the first time in more than a decade, patients with hepatocellular carcinoma (HCC) lived significantly longer with a new upfront therapy than with an existing standard of care.

The PD-L1 inhibitor atezolizumab (Tecentriq) plus the angiogenesis inhibitor bevacizumab (Avastin) reduced the survival hazard by 42% and the risk of disease progression by 41% as compared with the targeted VEGF inhibitor sorafenib (Nexavar) alone.

The median overall survival (OS) had yet to be reached in the combination arm as compared with a median OS of 13.2 months with sorafenib. Median progression-free survival was 6.8 months with the combination versus 4.3 months with sorafenib, as reported at the European Society for Medical Oncology Asia Congress in Singapore.

"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 has been the standard of care throughout this time," Ann-Lii Cheng, MD, of the National Taiwan University Cancer Center in Taipei, said in a statement. "Atezolizumab plus bevacizumab has the potential to be a practice-changing treatment option in hepatocellular carcinoma."

British oncologist Angela Lamarca, MD, PhD, of the Christie NHS Foundation Trust in Manchester, England, agreed with Cheng's assessment: "I think this is a breakthrough, and based on the results, the combination of atezolizumab could become the new standard of care," she said.

Ian Chau, MD, of the Royal Marsden Hospital in London, called the results "very encouraging," but noted that "with the high cost of immunotherapy and antiangiogenic agents, it will also be important that those drugs are accessible to patients."

Cheng reported the primary results of the phase III, randomized IMbrave150 trial, which involved 501 patients with unresectable HCC. Investigators in Asia, Europe, and North America randomized patients 2:1 to the combination or to single-agent sorafenib. The trial had co-primary endpoints of OS and PFS.

After a median follow-up of 8.6 months, patients in the atezolizumab-bevacizumab arm had a survival hazard ratio (HR) of 0.58 (P=0.0006) versus the sorafenib group and a PFS HR of 0.59 (P<0.0001). The combination produced objective responses in 27% of patients versus 12% with sorafenib by independent review (P<0.0001) and in 33% vs 13% by independent review of HCC-specific response criteria. Results were generally consistent across all prespecified subgroups, Cheng reported.

Rates of grade 3/4 adverse events were similar with the combination (57%) and sorafenib (55%), as were the rates of fatal adverse events (5% vs 6%). Atezolizumab plus bevacizumab also delayed deterioration in patient-reported quality of life as compared with sorafenib.

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