Atezolizumab plus bevacizumab improves survival outcomes vs. sorafenib in unresectable HCC
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Atezolizumab in combination with bevacizumab improved OS and PFS compared with sorafenib among patients with unresectable hepatocellular carcinoma, according to results of the randomized phase 3 IMbrave150 study published in The New England Journal of Medicine.
“Advanced HCC carries a poor prognosis, and [although] things have improved in the past few years with several new drug approvals, we have not had any improvement in OS in the first-line setting for over 12 years,” Richard S. Finn, MD, professor of medicine in the department of medicine, division of hematology/oncology, at David Geffen School of Medicine at University of California, Los Angeles, told Healio. “Standard treatment for patients like these is sorafenib [Nexavar; Bayer], which previously proved to be better than placebo. Recently, lenvatinib [Lenvima, Eisai] was approved for demonstrating noninferiority to sorafenib. No systemic therapy has been shown to improve OS vs. sorafenib since it was approved.”
HCC is a leading cause of cancer-related death globally. Early-stage disease can be cured through resection, liver transplantation or ablation. However, patients with later-stage disease that is unresectable have a poor prognosis.
The development and progression of liver cancer has been linked to several active intrinsic immune evasion pathways, including overexpression of VEGF. Anti-VEGF therapies, such as bevacizumab (Avastin, Genentech), have demonstrated an ability to reduce VEGF-mediated immunosuppression within the tumor and its microenvironment.
“There was interest in bevacizumab over a decade ago as a single agent in HCC, but the studies had mixed results in regard to efficacy and safety, and it never moved beyond phase 2,” Finn said. “There has been interest in immunotherapy in HCC. Nivolumab (Opdivo, Bristol-Myers Squibb), pembrolizumab (Keytruda, Merck) and ipilimumab (Yervoy, Bristol-Myers Squibb) in combination with nivolumab are all approved as second-line options based on phase 2 data.”
Several different immunotherapies that target the PD-L1/PD-1 pathway are being studied in HCC. They include atezolizumab (Tecentriq, Genentech), which selectively targets PD-L1 to block interaction with PD-1 and B7-1 and reverse T-cell suppression.
A previous phase 1b study showed atezolizumab in combination with bevacizumab induced antitumor activity in patients with unresectable HCC.
Finn and colleagues sought to assess the safety and efficacy of atezolizumab plus bevacizumab in a larger study.
The analysis included 501 patients with unresectable HCC who had no prior systemic treatment. Researchers assigned patients 2:1 to atezolizumab in combination with bevacizumab (n = 336) or sorafenib (n = 165). Treatment continued until unacceptable toxicity or loss of clinical benefit.
OS and PFS served as the study’s primary endpoints.
Median follow-up was 8.6 months, at which point 96 patients (28.6%) in the combination group and 65 patients (39.4%) in the sorafenib group had died (HR for death = 0.58; 95% CI, 0.42-0.79).
Researchers reported superior 12-month OS among patients assigned the combination (67.2%; 95% CI, 61.3-73.1) compared with sorafenib (54.6%; 95% CI, 45.2-64).
Median PFS was 6.8 months (95% CI, 5.7-8.3) in the combination group and 4.3 months (95% CI, 4-5.6) in the sorafenib group (HR for disease progression or death = 0.59; 95% CI, 0.47-0.76).
Grade 3 or grade 4 adverse events occurred among 56.5% of patients who received at least one dose of atezolizumab plus bevacizumab and 55.1% of patients who received at least one dose of sorafenib. The most common grade 3 or grade 4 adverse event, hypertension, occurred among 15.2% of patients in the combination group and 12.2% of patients in the sorafenib group.
“This will definitely become the standard of care for eligible patients,” Finn said. “In addition to OS, PFS was improved, response rates were significantly higher and durable, and the side effect profile and effects on quality of life were all better than the standard dose of sorafenib.”
For more information:
Richard S. Finn, MD, can be reached at University of California, Los Angeles, 2020 Santa Monica Blvd., Suite 600, Santa Monica, CA 90404; email: rfinn@mednet.ucla.edu.
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