From the Journals

‘Momentous’ data for first-line combo in liver cancer


New clinical data are set to change the treatment landscape for advanced liver cancer.

The data showed that atezolizumab plus bevacizumab improved survival, when compared with sorafenib, in patients with unresectable hepatocellular carcinoma (HCC).

The advanced liver cancer space has been dominated for a more than a decade by sorafenib (Nexavar, Bayer), which was the first systemic therapy to confer “a meaningful survival benefit in the treatment of advanced hepatocellular carcinoma,” notes Robin K. Kelley, MD, from the University of California, San Francisco.

“Since then, no treatment had surpassed the effect of sorafenib in the first line until the regimen of atezolizumab and bevacizumab” that is now being reported, she notes.

The new data come from the IMbrave150 study, published on May 14 in the New England Journal of Medicine.

“The combination of atezolizumab plus bevacizumab has become the new benchmark for first-line therapy in advanced hepatocellular carcinoma,” Kelley writes in an accompanying editorial.

“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,” she added.

The IMbrave 150 study was sponsored by Roche, manufacturer of both the checkpoint inhibitor atezolizumab (Tecentriq, Genentech/Roche) and the antiangiogenic agent bevacizumab (Avastin, Genentech/Roche); the company has submitted an FDA approval application for use of this combination for inoperable liver cancer.

“Results represent a breakthrough”

“These results represent a breakthrough in the management of advanced HCC,” said Josep M. Llovet, MD, PhD, director of the Mount Sinai Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, and professor of medicine in hepatic oncology at the University of Barcelona, Spain.

The combination has already been acknowledged as a milestone in the management of HCC, he said.

Llovet was approached for comment by Medscape Medical News. He was not involved with IMbrave150 but was the lead author on the SHARP study, which led to the first-line approval of sorafenib.

He explained that, since the approval of sorafenib in 2008, lenvatinib (Lenvima, Eisai) has been the only other agent approved for the front-line treatment of HCC after hitting the noninferiority endpoint for survival in comparison with sorafenib. “Up to now, there was no agent superior to sorafenib, the standard of care,” he said.

Now, the combination of atezolizumab-bevacizumab has shown superior efficacy compared with sorafenib, Llovet noted. It is not only the first combination to show efficacy but is also the first checkpoint inhibitor that has demonstrated efficacy in HCC. “Previous studies of checkpoint inhibitors used as single agents in the front-line or second-line setting of advanced liver cancer were negative,” he said.

“Game-changer” in liver cancer

“The atezolizumab-bevacizumab combination is a game-changer in liver cancer,” the lead author of the IMbrave 150 trial, Richard S. Finn, MD, of the David Geffen School of Medicine at the University of California, Los Angeles, told Medscape Medical News.

“The combination has established a new standard of care that is predicated on the gold standard of overall survival [OS] and is underscored by prolonged progression-free survival [PFS] and high response rates that are durable,” Finn said.

In the IMbrave150 trial, treatment-naive patients who had unresectable liver cancer received either atezolizumab-bevacizumab (n = 336) or sorafenib (n = 165).

After a median follow-up of 8.6 months, median survival was significantly longer for the patients who received atezolizumab-bevacizumab: 13.2 months. For the patients who did not receive the combination, median survival was not reached (hazard ratio [HR], 0.58; P < .001). Six-month OS was 84.8% with the combination versus 72.2% with sorafenib.

Median PFS was also significantly longer for patients who received combination therapy: 6.8 months with the combination versus 4.3 months with sorafenib (HR, 0.59; P < .001). Six-month PFS was 54.4% with the combination versus 37.3% with sorafenib.

The objective response rate was 27.3% (complete response, 5.5%) with the combination versus 11.9% (complete response, 0%) with sorafenib

Median time to deterioration of quality of life was also longer for patients who received combination therapy: 11.2 months with atezolizumab-bevacizumab and 3.6 months for sorafenib.

Incidence of grade 3 or 4 adverse events was similar in both arms of the study: 56.5% for the combination versus 55.1% with sorafenib. Adverse events leading to withdrawal from any study drug was not significantly different: 15.5% versus 10.3% for sorafenib.

The percentage of patients who experienced bleeding of any grade (attributed to bevacizumab) was 25.2% with the combination versus 17.3% with sorafenib. In addition, six incidents of fatal bleeding or perforated ulcer were recorded in the combination group, compared with one for the sorafenib group.

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