Cabozantinib phase 3 results show overall survival benefit for liver cancer

Exelixis and Ipsen announced results from the phase 3 Celestial trial of cabozantinib for hepatocellular carcinoma that showed significant overall survival benefit in patients previously treated for advanced HCC, according to a press release and data presented at the 2018 ASCO-GI Symposium in San Francisco.

“Patients with advanced hepatocellular carcinoma often have a poor prognosis and limited treatment options following prior systemic therapy,” Ghassan K. Abou-Alfa, MD, from the Memorial Sloan Kettering Cancer Center, New York, and lead investigator of the Celestial trial, said in the release. “The clinically significant benefits in both overall survival and progression-free survival shown in the Celestial trial suggest that, if approved, cabozantinib could become an important addition to the treatment landscape for these patients.”

The researchers enrolled 760 patients with advanced HCC and prior treatment from more than 100 sites across 19 countries in the randomized, double-blind, placebo-controlled study.

Median overall survival in patients who received cabozantinib was 10.2 months compared with 8 months for those who received placebo (HR = 0.76; 95% CI, 0.63-0.92). Median progression-free survival was 5.2 months in the treatment group compared with 1.9 months in the placebo group (HR = 0.44; 95% CI, 0.36-0.52).

Response rates per Response Evaluation Criteria in Solid Tumors were 4% in the treatment group and 0.4% in the placebo group (P = .0086). Partial response or stable disease rates were 64% in the treatment group and 33% in the placebo group.

In a subgroup analysis of patients whose sole treatment experience was Nexavar (sorafenib, Bayer Pharmaceuticals), median overall survival was 11.3 months in patients who received cabozantinib compared with 7.2 months in those who received placebo (HR = 0.7; 95% CI, 0.55-0.88). Median progression-free survival in the subgroup analysis was 5.5 months in the treatment group and 1.9 months in the placebo group (HR = 0.4; 95% CI, 0.32-0.5).

According to the researchers, adverse events were consistent with the known safety profile of cabozantinib. The most common grade 3 or 4 adverse events in the treatment group, compared with the placebo group, included palmar-plantar erythrodysesthesia (17% vs. 0%), hypertension (16% vs. 2%), increased aspartate aminotransferase (12% vs. 7%), fatigue (10% vs. 4%) and diarrhea (10% vs. 2%).

Five patients experienced treatment-related grade 5 adverse events including hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism and hepatorenal syndrome, compared with one patient in the placebo group who experienced hepatic failure. The rate of discontinuation due to adverse events was 16% in the treatment group and 3% in the placebo group.

“We are excited by the potential benefit cabozantinib may offer to patients with previously treated advanced hepatocellular carcinoma,” Gisela Schwab, MD, president of product development and medical affairs and chief medical officer at Exelixis, said in the release. “Given the worldwide prevalence of advanced hepatocellular carcinoma, there is a continued urgency to bring new treatment options to this patient population. We look forward to submitting our supplemental new drug application to the FDA for cabozantinib in the first quarter of 2018, and to further advancing our mission to help cancer patients recover stronger and live longer.” – by Talitha Bennett

Disclosure: Healio.com/Hepatology was unable to determine relevant financial disclosures at the time of publication.