GI cancer

‘Momentous’: checkpoint inhibitor combo is new benchmark for first-line therapy in advanced HCC


The first therapy to improve survival beyond sorafenib in advanced liver cancer has bee hailed as a landmark in treatment of the disease.

A combination of atezolizumab plus bevacizumab improved survival in patients with unresectable liver cancer compared to treatment with sorafenib, according to an international study across 17 countries including Australia.

An open-label, phase 3 trial in 501 patients with hepatocellular carcinoma (HCC) randomised to either the PD-L1 and VEGF inhibitor combination or sorafenib found early and enduring survival benefit with the combination.

Overall survival at 12 months was 67.2% with the combination treatment and 54.6% with sorafenib. Median progression free survival was also significantly longer with atezolizumab plus bevacizumab compared with sorafenib (6.8 v 4.3 months).

The study found the OS and PFS benefits with atezolizumab–bevacizumab as compared with sorafenib were generally consis­tent across the clinically relevant subgroups.

It also found the con­firmed objective response rates were 27.3% with atezolizumab–bevacizumab compared to 11.9% with sorafenib.

“The estimated percentage of patients with duration of response longer than 6 months was 87.6% in the atezolizumab–bevacizumab group and 59.1% in the sorafenib group,” the study authors said.

And treatment with the new combination delayed deterioration of patient-reported quality of life (11.2 v 3.6 months), physical functioning (13.1 v 4.9 months) and role functioning (9.1 v 3.6 months).

Serious adverse events occurred more frequently with atezolizumab– bevacizumab than with sorafenib (38.0% v 30.8%) and discontinuation due to toxicity was higher with the combination (15.5% v 10.3%).

Writing in the NEJM, the study investigators said the findings showed the clinical benefit of targeting both angiogenesis and PD-­L1 signalling in unresect­able liver cancer.

“The early separation of the Kaplan–Meier curves for overall survival was maintained over time despite a higher propor­tion of patients in the sorafenib group receiving subsequent systemic therapy, including immuno­therapy,” they said.

An accompanying editorial in the journal said the combination was a new benchmark for first-line therapy in advanced HCC.

“These data are momentous, since they identify not only the first therapy to improve survival beyond sorafenib, but also the first successful combination regimen and the first positive randomized, phase 3 trial of immune checkpoint inhibition in this challenging cancer.”

However there were still more questions to be answered, including management of patients with varices who were excluded from the study, biomarkers for response to immune checkpoint inhibitors, and the various benefits of sequential versus upfront combination therapy.

A number of phase 3 trials planned or underway – here, here, here and here – should help provide some of the answers, they said.

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