On May 29, Roche announced that the FDA had approved Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) as a first-line treatment for unresectable or metastatic hepatocellular carcinoma (HCC) in patients who have not received prior systemic therapy.
This FDA approval is primarily based on the results of the Phase III IMbrave150 study. The multicenter, open-label IMbrave150 study enrolled 501 patients with unresectable or metastatic hepatocellular carcinoma (HCC) who had not received prior systemic therapy. Patients were randomized in a 2:1 ratio to receive either Tecentriq (1200 mg once every 3 weeks) plus Avastin (15 mg/kg once every 3 weeks) or sorafenib (400 mg twice daily), until disease progression or unacceptable toxicity. The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS) assessed by independent review facility (IRF) according to RECIST v1.1 criteria.
The results showed that, compared with sorafenib as first-line therapy, Tecentriq plus Avastin reduced the risk of death by 42% (HR=0.58; 95% CI: 0.42-0.79; p=0.0006) and reduced the risk of disease progression or death by 41% (HR=0.59; 95% CI: 0.47-0.76; p<0.0001). The incidence of grade 3–4 serious adverse events in the Tecentriq plus Avastin group was 38%; the most common (≥2%) serious adverse reactions included gastrointestinal hemorrhage, infection, and pyrexia.
Liver cancer is a common and high-incidence malignancy. Globally, there are approximately 854,000 new cases of liver cancer annually, with 466,000 cases in China, accounting for half of the global total. Each year, 810,000 patients worldwide die from liver cancer, including 422,000 in China. According to estimates by the American Cancer Society, more than 42,000 people in the United States were diagnosed with liver cancer in 2020. Since 1980, the incidence rate of liver cancer has more than tripled. Hepatocellular carcinoma (HCC) accounts for approximately 75% of all liver cancer cases in the United States. The primary risk factors for liver cancer are chronic hepatitis (hepatitis B and hepatitis C) or cirrhosis caused by excessive alcohol consumption. Patients are often diagnosed at an advanced stage, when treatment options are limited.
The current first-line standard therapies for liver cancer are primarily sorafenib-targeted therapy or the FOLFOX chemotherapy regimen containing oxaliplatin. In the more than 10 years since sorafenib's approval, no drug has managed to "head-to-head" defeat sorafenib in first-line treatment. Opdivo (O drug) and Keytruda (K drug) were also accelerated approved as second-line treatments for liver cancer, but they failed to meet their preset endpoints in post-marketing confirmatory studies, ultimately ending in failure.
The combination regimen of Tecentriq plus Avastin has broken the decade-long stalemate in first-line treatment for hepatocellular carcinoma, delivering the best efficacy observed to date in Phase III clinical studies of first-line systemic therapy for unresectable hepatocellular carcinoma. It is also the first novel first-line therapy in over ten years to surpass the current standard of care, sorafenib, in a Phase III clinical trial.