Despite a government shutdown, the FDA approved cabozantinib (Cabometyx) as a treatment for patients with hepatocellular carcinoma (HCC) who previously received sorafenib (Nexavar).
The approval was based on findings from the phase III CELESTIAL trial, in which overall survival (OS) was improved by 2.2 months with cabozantinib versus placebo. Median OS with cabozantinib was 10.2 versus 8.0 months for placebo, representing a 24% reduction in the risk of death.
“Patients with this form of advanced liver cancer have few treatment options, particularly once their disease progresses following treatment with sorafenib,” CELESTIAL trial lead investigator Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center, said in a company press release.
“Physicians are eager for new options for these patients, and the results of the CELESTIAL trial demonstrate that Cabometyx has the efficacy and safety profile to become an important new therapy in our efforts to slow disease progression and improve treatment outcomes.”
In the trial, 707 patients were randomized to receive cabozantinib at 60 mg daily (n = 470) or placebo (n = 237). All patients had an ECOG performance status of 0 or 1, a Child-Pugh score of A, and had progressed on at least 1 prior systemic therapy for advanced HCC, with 70% having received only prior sorafenib (Nexavar).
Baseline characteristics were balanced between the arms. The median age was 64 years and 82% were male. The baseline etiologies included hepatitis B virus infection (38%) and hepatitis C virus infection (24%). Over three-fourths of patients had extrahepatic spread (78%) and 30% had macrovascular invasion, with 27% of patients having both. A quarter of patients were enrolled in Asia (25%) and 27% had received 2 prior systemic therapies.
The median progression-free survival (PFS) was 5.2 months compared with 1.9 months for placebo, which was a 56% reduction in the risk of progression or death with the targeted therapy (HR, 0.44, 95% CI, 0.36-0.52; P <.0001). The objective response rate (ORR) was 4% with cabozantinib compared with 0.4% with placebo (P = .0086). When including those with stable disease, the disease control rate with the multikinase inhibitor was 64% compared with 33% for placebo.
“This new indication for Cabometyx is an important treatment advance for patients with this aggressive form of liver cancer, a community in need of new therapeutic options,” Michael M. Morrissey, PhD, president and chief executive officer of Exelixis, said in a statement. “This approval is an important milestone as we continue to explore how Cabometyx may benefit people with difficult-to-treat-cancers beyond renal cell carcinoma. We would like to thank the patients and clinicians who participated in CELESTIAL and to acknowledge the team at the FDA for their continued collaboration during the review of our application.”
Cabozantinib was first approved by the FDA as a treatment for patients with medullary thyroid cancer in 2012. It received a new indication for advanced renal cell carcinoma (RCC) in 2016. This approval was expanded in December 2017 to include the treatment of patients with advanced RCC in the first-line setting.