FDA Grants Atezolizumab Combo Breakthrough Designation for Frontline HCC

Sandra Horning, MD

The FDA has granted atezolizumab (Tecentriq) a breakthrough therapy designation for use in combination with bevacizumab (Avastin) as a first-line treatment for patients with advanced or metastatic hepatocellular carcinoma (HCC).

The designation, which will expedite the development and review of the combination in this setting, is based on a phase Ib study in which independent reviewers determined that at a median follow-up of 10.3 months, atezolizumab/bevacizumab induced an overall response rate (ORR) of 65% (n = 15) among 23 evaluable patients. Genentech, the manufacturer of both agents, reported in a press release that responses were observed across patient subgroups defined by etiology, geography, baseline AFP levels, and extrahepatic spread.

“Hepatocellular carcinoma is an aggressive cancer with limited treatment options and a major cause of cancer deaths worldwide,” Sandra Horning, MD, chief medical officer and head of Global Product Development, Genentech, said in a statement. “Preliminary data from the combination of Tecentriq and Avastin in this disease are promising and we look forward to working with health authorities to make this potential treatment regimen available to people with hepatocellular carcinoma as soon as possible.”

The median age among the 23 patients in the efficacy evaluable population was 62 (range, 35-78). Eighteen patients were male and 5 were female. Fourteen patients were from the United States or Japan, and 9 patients were from areas in Asia outside of Japan. Ten patients had an ECOG performance status of 0 and the remaining 13 patients had a status of 1.

The Child Pugh class for the 23 patients was A5 (n = 17), A6 (n = 5), or B7 (n = 1). Ten patients had the hepatitis B virus (HBV), 9 had the hepatitis C virus (HCV), and 4 had non-viral disease. Ten patients had TNM stage IVb disease and 11 patients had extrahepatic spread. Baseline AFP levels were measured at <200 ng/mL (n = 11), 200 to 400 ng/mL (n = 2), and ≥400 ng/mL (n = 9). The baseline AFP value was missing for 1 patient in the efficacy population.

Patients received 1200 mg of atezolizumab IV and 15 mg/kg of bevacizumab IV every 3 weeks until unacceptable toxicity or loss of clinical benefit.

The 65% ORR comprised a complete response rate of 4% (n = 1) and a partial response rate of 61% (n = 14). Additionally, 7 (30%) patients had stable disease and 1 (4%) patient had progressive disease. A disease control rate of ≥6 months was reported for 16 (70%) patients.

The ORR was 60% in HBV-positive patients, 78% in HCV-positive patients, and 50% in non-viral patients. In US/Japanese and Asian (non-Japanese) patients, the ORRs were 65% and 67%, respectively. Among the patients with low, intermediate, and high AFP levels, the ORRs were 55%, 100%, and 78%, respectively. Patients with and without extrahepatic spread had ORRs of 73% and 75% respectively.

The safety population included all 43 patients who received any amount of study treatment. Treatment-related grade 3/4 adverse events occurred in 28% (n = 12) of patients, with the most common being hypertension (n = 7). There were no treatment-related deaths.

The ongoing phase III IMbrave150 study (NCT03434379) is comparing atezolizumab/bevacizumab with sorafenib (Nexavar) in the frontline setting for patients with locally advanced or metastatic HCC.

Stein S, Pishvaian MJ, Lee MS, et al. Safety and clinical activity of 1L atezolizumab + bevacizumab in a phase Ib study in hepatocellular carcinoma (HCC). J Clin Oncol. 2018;36 (suppl; abstr 4074).