A newly published study discussed the potential for the anti–vascular endothelial growth factor agent bevacizumab (Avastin) and its cost-saving biosimilars to be used as second-line therapy for the treatment of patients with advanced hepatocellular carcinoma (HCC) who progressed while receiving standard therapy.
Hepatocellular carcinoma (HCC) has associated 5-year overall survival (OS) of less than 20%, and HCC mortality rates have increased in the past decades, largely due to a lack of effective therapies. A newly published study discussed the potential for the anti—vascular endothelial growth factor (VEGF) agent bevacizumab (Avastin) and its cost-saving biosimilars to be used as second-line therapy for the treatment of patients with advanced HCC who progressed while receiving standard therapy.
Prior to 2017, sorafenib, an oral multikinase inhibitor that has activity against VEGF signaling, was the only FDA-approved agent for treating advanced HCC. In 2017, regorafenib, another oral agent with activity against VEGF signaling, received approval in advanced HCC for patients who progressed while receiving sorafenib, and the FDA recently approved lenvatinib, which acts against multiple VEFG receptors, for first-line treatment. While the effectiveness of these therapies provides a rationale for testing other anti-VEGF agents in HCC, no phase 3 trials of bevacizumab have yet been undertaken in this setting.
In a study published this week in Cancer Medicine, researchers from a single Veterans Affairs (VA) center reported on the use of bevacizumab as an off-label second-line agent for patients with advanced HCC who either were intolerant to sorafenib or whose disease had progressed while taking the drug.
Between 2014 and 2018, 12 patients at the center received bevacizumab for advanced HCC. Largely consistent with the veteran liver cancer population, patients were all males and of a median age of 62 years (range, 55-71). All patients had received prior locoregional therapy, and 92% had also received systemic therapy.
The patients received bevacizumab as monotherapy during the study period; 4 patients received 5 mg/kg every 2 weeks, 4 patients received 7.5 mg per kg every 3 weeks, and 4 patients received 10 mg per kg every 2 weeks. OS was measured as the time from the start of bevacizumab until death.
Median OS was 20.2 months (range, 0.7-44.1 months), and 5 of the 12 patients remained alive at the time of censoring with a median of 13.1 months of bevacizumab exposure. At the time of analysis, 10 patients had either developed progression or had died, and 1 patient had ongoing partial response (3 patients total achieved partial response during the study period, and 3 achieved stable disease; no patients had a complete response). The median time to progression was 10.4 months (range, 0.7-27.3 months).
The median duration of treatment was 8.5 months (range, 0.5‐42 months), and the most common reason for discontinuation was disease progression. Two patients discontinued the treatment due to adverse events.
“Although the small study size and heterogeneous population limit definitive conclusions, the clinical benefit in this retrospective analysis was greater than expected,” write the authors, adding that the cost-effectiveness of bevacizumab will be positively impacted by biosimilar options (the FDA approved Amgen’s Mvasi in 2017, and the European Medicines Agency has approved both Mvasi and Pfizer’s biosimilar, Zirabev).
While further study will be needed to determine the efficacy of bevacizumab in this setting, “our findings suggest that bevacizumab is potentially a viable therapeutic option for advanced HCC,” write the authors.
Wattenberg MM, Damjanov N, Kaplan DE. Utility of bevacizumab in advanced hepatocellular carcinoma: A veterans affairs experience [published online February 20, 2019]. Cancer Medicine. doi: 10.1002/cam4.2015.