The Food and Drug Administration has approved a regimen combining the immune checkpoint inhibitor Tecentriq (atezolizumab) and the targeted therapy Avastin (bevacizumab) for the treatment of people with inoperable or metastatic hepatocellular carcinoma, the most common type of liver cancer.
In the Phase III IMbrave150 study, Tecentriq plus Avastin reduced the risk of disease progression or death by 41%, prolonged overall survival and improved quality of life compared with standard-of-care treatment.
Over years or decades, chronic hepatitis B or C, heavy alcohol use, fatty liver disease and other causes can lead to the development of liver cirrhosis and HCC. Liver cancer is often detected late and is difficult to treat, making it one of the leading causes of cancer-related death.
The IMbrave150 trial (ClinicalTrials.gov number NCT03434379) included 501 people with inoperable locally advanced or metastatic liver cancer who had not yet received systemic treatment. They were randomly assigned to receive Tecentriq plus Avastin, both administered by IV infusion every three weeks, or twice-daily oral Nexavar (sorafenib) until they experienced disease progression or unacceptable side effects.
Tecentriq is a PD-L1 checkpoint inhibitor that restores T-cell activity against cancer. Avastin is a monoclonal antibody that blocks VEGF, a protein that promotes the proliferation of blood vessels that supply tumors and plays a role in immune suppression. Nexavar is a multikinase inhibitor that blocks the action of several enzymes, including VEGFR, BRAF and RET, involved in cell growth pathways.
Primary results from the study were presented at the European Society for Medical Oncology Asia Congress last November, showing that Tecentriq plus Avastin reduced the risk of disease progression or death by 41% (median 6.8 versus 4.3 months). Overall survival was 13.2 months in the Nexavar group but was not reached in the combination therapy group because most patients were still alive. Overall response rates, meaning complete or partial tumor shrinkage, were 28% versus 12%, respectively.
At the American Society of Clinical Oncology Gastrointestinal Cancers Symposium in January, researchers reported that Tecentriq plus Avastin led to improved quality of life and delayed worsening of symptoms.
Tecentriq plus Avastin recipients reported about a 30% decline in their quality of life, compared with about a 40% decline among Nexavar recipients. A similar pattern was seen for physical functioning and role functioning. For all three measures, the time to deterioration was substantially longer for those taking the combination regimen. Those using Tecentriq plus Avastin also reported a longer period before they experienced worsening of symptoms including loss of appetite, diarrhea, fatigue and pain.
The most common adverse reactions among people taking Tecentriq plus Avastin group are hypertension, fatigue and protein in the urine. IMbrave150 participants who used Tecentriq plus Avastin were more likely to experience fever, abnormal liver and kidney biomarkers and infusion reactions, while those taking Nexavar had more diarrhea and hand-foot syndrome (redness, swelling and pain on the palms of the hands and soles of the feet).
The recommended dose of Tecentriq is 1,200 milligrams mg, followed by 15 mg per kilogram of Avastin administered on the same day every three weeks. If Avastin is discontinued, Tecentriq should be given either as 840 mg every two weeks, 1,200 mg every three weeks or 1,680 mg every four weeks.
“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,” Richard Finn, MD, of the David Geffen School of Medicine and the UCLA Jonsson Comprehensive Cancer Center said in a Genentech press release. “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.”