The FDA has granted a breakthrough therapy for atezolizumab Tin combination with bevacizumab for the treatment of advanced or metastatic hepatocellular carcinoma.
The US Food and Drug Administration (FDA) has granted a breakthrough therapy designation to Roche for atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) as a first-line treatment for patients with advanced or metastatic hepatocellular carcinoma (HCC), the most common form of liver cancer and known to appear in patients with chronic hepatitis B and C.
"Hepatocellular carcinoma is an aggressive cancer with limited treatment options and a major cause of cancer deaths worldwide," Sandra Horning, MD, Roche's chief medical officer and head of global product development, stressed in a recent statement.
Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. Bevacizumab is a biologic antibody engineered to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis.
Bevacizumab’s established anti-angiogenic effects may further enhance atezolizumab’s ability to restore anti-cancer immunity by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumor infiltration, and enabling priming and activation of T-cell responses against tumor antigens.
Data from the open-label, multicenter phase 1b study evaluating the safety and clinical activity of the atezolizumab-bevacizumab combination served as the basis for the designation.
For the study, participants in Study Arm A are receiving atezolizumab (1200 mg) and bevacizumab (15 mg/kg) intravenously (IV) every 3 weeks until loss of clinical benefit or unacceptable toxicity. Primary objectives from Arm A include assessing the clinical activity, based on objective response rate (ORR) assessment by independent review facility (IRF) per RECIST v1.1 as well as evaluating the safety and tolerability of the combination.
The objective response rate (ORR) by investigator assessment (INV), progression-free survival (PFS), duration of response (DOR), time to progression (TTP) all by INV and IRF per RECIST v1.1; and overall survival (OS) compose the secondary efficacy endpoints.
Findings presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, revealed responses (independent review facility (IRF) per RECIST v1.1) noted in 15 of 23 (65%) efficacy-evaluable patients, after a median follow-up of 10.3 months; these responses were seen across all subgroups (etiology, region, baseline alpha-fetoprotein levels, spread of tumor beyond liver). INV per RECIST v1.1 also showed response in 14 out of 23 patients (61%). Median PFS, DOR, TTP, and OS have not been reached yet after the median follow-up; these results will be presented at a future conference as the data becomes available.
Safety measured were also reported. Twenty-eight percent of patients (n=12) in the safety-evaluable population (n=43) experienced Grade 3-4 treatment-related adverse events; however, no treatment-related Grade 5 adverse events were observed, and no new safety signals were identified beyond the established safety profiles for the individual medicines.
"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,” Dr Horning added.
Moving forward, IMbrave150, an open-label, multicenter, randomized phase 3 study investigating the combination of atezolizumab and bevacizumab versus sorafenib in individuals with previously-untreated (first-line) locally advanced, unresectable or metastatic HCC, was initiated earlier this year and is currently enrolling participants.