IMbrave150: atezolizumab plus bevacizumab replaces sorafenib as first treatment for advanced liver cancer
Combining the immunotherapy atezolizumab with the anti-blood-vessel antibody bevacizumab helped patients with advanced hepatocellular carcinoma live longer than sorafenib, ending a decade in which nothing had beaten that drug.
Open-label phase 3 trial of 501 patients with unresectable hepatocellular carcinoma and preserved liver function (Child-Pugh A) who had not received systemic therapy, randomised 2:1 to atezolizumab plus bevacizumab or sorafenib. Co-primary endpoints were OS and PFS.
12-month OS was 67.2% vs 54.6% (HR 0.58) and median PFS 6.8 vs 4.3 months (HR 0.59). The updated analysis showed median OS 19.2 vs 13.4 months (HR 0.66). It made atezolizumab plus bevacizumab the first-line standard, showed that immunotherapy combinations can work in liver cancer despite the failure of single-agent checkpoint inhibitors, and set the template for durvalumab plus tremelimumab (HIMALAYA).
- 12-month overall survival 67.2% vs 54.6%; HR 0.58 (95% CI 0.42-0.79).
- Median PFS 6.8 vs 4.3 months; HR 0.59.
- Objective response 27.3% vs 11.9% (RECIST 1.1).
- Updated analysis (2022): median OS 19.2 vs 13.4 months, HR 0.66; median PFS 6.9 vs 4.3 months.
- Grade 3-4 adverse events similar (57% vs 55%); upper gastrointestinal bleeding with bevacizumab required endoscopic screening for varices within six months before enrolment.
- Patient-reported quality of life deteriorated later with the combination (11.2 vs 3.6 months).
Patients with advanced liver cancer and good liver function should be offered atezolizumab plus bevacizumab (or durvalumab plus tremelimumab) rather than sorafenib as first treatment; median survival is now around 19 months and about a quarter of patients respond. Endoscopy to treat varices before starting bevacizumab is essential because of bleeding risk. Patients with poorer liver function (Child-Pugh B) or autoimmune disease or transplants were not studied.
- Excluded Child-Pugh B, untreated varices, and prior transplant, so applies to a selected population.
- Open-label; sorafenib is now a weak comparator.
- Non-viral (metabolic) liver cancer appeared to benefit less in exploratory analyses across several immunotherapy trials.
- Bleeding and hypertension from bevacizumab, and cost, remain barriers in high-incidence low-income regions.