Cabometyx-Tecentriq Combo Bests Nexavar in Controlling Disease, Limiting Progression in Patients With Advanced Liver Cancer

The use of Cabometyx (cabozantinib) plus Tecentriq (atezolizumab) significantly improved progression-free survival — which is the length of time a person lives without disease progression — and increased disease control rates versus Nexavar (sorafenib) alone in patients with advanced hepatocellular carcinoma, according to recently published study findings.

The data, according to the study authors, demonstrate that the combination of Cabometyx and Tecentriq may be a viable treatment option for certain patients with advanced hepatocellular carcinoma, the most common type of liver cancer.

“For some patients, delaying progression and achieving rapid disease control is particularly important, such as in symptomatic patients with high disease burden or main portal vein occlusion at risk for impending complications,” the study authors wrote in the manuscript printed in The Lancet Oncology. “The observed improvement in progression-free survival in subgroups with more advanced malignancy, including those with extrahepatic disease or macrovascular invasion, reinforces the assessment of clinical benefit.”

The findings, however, also showed that the combination failed to improve overall survival (time a patient is alive without death from any cause) compared with single-agent Nexavar or Tecentriq.

“At interim analysis of overall survival presented here, an early separation … was seen, but overall survival did not differ significantly between the treatment groups,” the authors wrote. “Final overall survival analyses will be presented along with updated safety data in a future publication.”

Prior investigations have shown that treatment with tyrosine kinase inhibitors — of which Cabometyx is classified as — combined with immune checkpoint inhibitors have been effective in other solid tumor types, including kidney cancer. In fact, the Food and Drug Administration approved the combination of Cabometyx and the immune checkpoint inhibitor Opdivo (nivolumab) as a first-line treatment option for advanced kidney cancer.

The agency based its decision to approve the combination in January 2021 based on findings from the phase 3 CheckMate-9ER study, which demonstrated that Cabometyx plus Opdivo significantly improved survival versus Sutent (sunitinib) alone.

This approach, the study authors noted, had not yet been reviewed in a phase 3 trial in patients with hepatocellular carcinoma. To assess the efficacy and safety of combining a tyrosine kinase inhibitor with an immune checkpoint inhibitor in this patient population, the investigators randomized 837 patients to receive the combination of Cabometyx and Tecentriq (432 patients), Nexavar alone (217 patients) or Cabometyx alone (188 patients).

At a median follow-up of 15.8 months for the first 372 patients randomly assigned to the combination and 13.3 months for the entire study population, median progression-free survival was 6.8 months for the group that received Cabometyx and Tecentriq and 4.2 months for those who were given Nexavar.

Moreover, six-month progression-free survival was 54.5% in the combination treatment group versus 40% in the Nexavar group. The progression-free survival continued to favor Cabometyx and Tecentriq at month 12 — 28.5% versus 18% for Nexavar.

At the interim analysis, median overall survival was 15.4 months in the combination group compared with 15.5 months in single-agent Nexavar.

Treatment-related side effects of any severity occurred in 93% of patients in the Cabometyx-Tecentriq combination group, 90% of the Nexavar group and 95% in the single-agent Cabometyx group.

“The phase 3 COSMIC-312 study had dual primary endpoints of progression-free survival and overall survival for (Cabometyx) plus (Tecentriq) versus (Nexavar) as first-line systemic treatment for patients with advanced hepatocellular carcinoma not amenable to curative treatment or locoregional therapy,” the authors concluded. “Primary progression-free survival was significantly longer in the combination treatment group versus the (Nexavar) group.”

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