The U.S. Food and Drug Administration (FDA) approved Genentech’s checkpoint inhibitor Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) for unresectable or metastatic hepatocellular carcinoma (HCC) who haven’t received previous systemic therapy. Tecentriq is an anti-PD-L1 checkpoint inhibitor. Avastin binds to the VEGF protein, which plays a significant role in the development and maintenance of blood vessels by cancer cells.
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with about 42,000 people diagnosed with liver cancer in the U.S. this year, and about 75% of it being HCC. It is found mostly in patients with cirrhosis caused by chronic hepatitis B and C or alcohol consumption.
“We’re excited that today’s approval of Tecentriq in combination with Avastin for unresectable or metastatic hepatocellular carcinoma brings a cancer immunotherapy option to people with this aggressive form of liver cancer,” said Levi Garraway, Genentech’s chief medical officer and head of Global Product Development. “The application was reviewed under the FDA’s Real-Time Oncology Review pilot and Project Orbis initiative, helping to bring this new treatment option rapidly to patients in the United States and around the world.”
Project Orbis offers a framework for concurrent submission and review of cancer drugs among international partners. This allows patients diagnosed with cancer to receive earlier access to drugs in other countries that would otherwise have delays in regulatory submissions. Applications were submitted simultaneously to regulators in the U.S., Australia, Canada and Singapore under Project Orbis. The FDA also quickly reviewed and approved the application under its Real-Time Oncology Review (RTOR) pilot program.
The approval was based on data from the Phase III IMbrave 150 trial. This study showed that Tecentriq in combination with Avastin decreased the risk of death, or the overall survival (OS) by 42%, and reduced the risk of the cancer getting worse or death, called progression-free survival (PFS), by 41% compared with sorafenib. Sorafenib is marketed by Bayer under the trade name Nexavar.
Serious side effects of Grade 3-4 were observed in 38% of people in the Tecentriq and Avastin arm. The most frequent serious adverse reactions were bleeding in the GI tract, infections and fever.
IMbrave150 evaluated 501 people with unresectable or metastatic HCC who had not received previous therapy. They were randomized 2:1 to receive the combination therapy or sorafenib. The two primary endpoints were OS and independent review facility (IRF)-assessed PFS per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
“The results of the IMbrave150 study are really transformative for patients with advanced liver cancer, one of the few cancers with a rising death rate and limited options in the first-line setting,” said Richard Finn, professor of Medicine at the David Geffen School of Medicine at UCLA and director of the Signal Transduction and Therapeutics Program at the UCLA Jonsson Comprehensive Cancer Center. “For the first time we have a regimen that markedly improves survival over sorafenib, the standard of care for first-line hepatocellular carcinoma since 2007, and offers patients the opportunity for improved disease control with a favorable tolerability profile.”
The new data for the IMbrave150 study was published on May 14 in the New England Journal of Medicine with an accompanying editorial by Robin K. Kelley from the University of California, San Francisco.
“The combination of atezolizumab plus bevacizumab has become the new benchmark for first-line therapy in advanced hepatocellular carcinoma,” Kelly wrote. “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 III trial of immune checkpoint inhibition in this challenging cancer.”
Medscape Medical News, covering the publication of the data in mid-May, approached Josep M. Llovet, director of the Mount Sinai Liver Cancer Program, Icahn School of Medicine at Mount Sinai and professor of medicine in hepatic oncology at the University of Barcelona, Spain, for comment. 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 stated, “These results represent a breakthrough in the management of advanced HCC. Up to now there was no agent superior to sorafenib, the standard of care.”