Frontline treatment with Opdivo improved overall survival and response rates among patients with advanced hepatocellular carcinoma, however, the trial missed its primary endpoint.
Frontline treatment with Opdivo (nivolumab) improved overall survival and response rates among patients with advanced hepatocellular carcinoma, compared with Nexavar (sorafenib), according to results from the CheckMate 459 study.
Moreover, the targeted therapy showed a favorable safety profile compared with the current standard of care.
“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Thomas Yau, from the University of Hong Kong, said in a press release issued by the European Society of Medical Oncology. “(Hepatocellular carcinoma) is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”
Unfortunately, the study did not meet its prespecified primary endpoint for improved overall survival. However, Yau explained, the primary analysis demonstrated a clinically meaningful overall survival benefit, “which is particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy in the sorafenib arm. Importantly, there was also a higher complete response rate with nivolumab compared to sorafenib,” he added.
Moreover, Yau noted, patients treated with Opdivo experienced improved quality of life and may support the clinical benefit of the drug.
In the phase 3 CheckMate 459 study, the researchers randomized 743 patients to either frontline Opdivo or Nexavar.
Patients treated with Opdivo experienced a median overall survival of 16.4 monhts, compared with 14.7 months in those treated with Nexavar.
Of note, clinical benefit was observed among predefined subgroups of patients with hepatitis infection and those with vascular invasion and/or extrahepatic spread, according to the press release.
The overall response rate was 15% for those treated with Opdivo, and included 14 patients who experienced a complete response, compared with 7% of those treated with Nexavar, and included five patients with a complete response.
Less patients in the Opdivo arm experienced side effects from treatment, compared with Nexavar (22% vs. 49%), which led to discontinuation in 4% and 8%, respectively.
Dr. Angela Lamarca, from the Christie NHS Foundation Trust in Manchester, commented on the study findings, saying that, although the trial did not meet its primary endpoint, “it is becoming more apparent that immunotherapy could have a role for the first-line treatment of advanced (hepatocellular carcinoma) and the differences in response rates are clinically meaningful.”
She also noted that the favorable safety profile is of relevance: “(This) becomes apparent in the form of less toxicity-related treatment discontinuation with nivolumab,” Lamarca said, adding that the significance in improved quality of life is equally important.
“In a hypothetical scenario in which both options (sorafenib and immunotherapy) were available and reimbursed, and if quality of life was shown to be better with nivolumab (because of the better safety profile compared to sorafenib suggested in this study), clinicians and patients may favor the option with a more tolerable safety profile.”