{"id":27746,"date":"2021-12-22T08:41:00","date_gmt":"2021-12-22T08:41:00","guid":{"rendered":"http:\/\/8c8ad1b9507c57b1829399988c2e9189"},"modified":"2024-11-03T15:14:06","modified_gmt":"2024-11-03T15:14:06","slug":"nivolumab-does-not-prolong-overall-survival-compared-with-sorafenib-in-first-line-treatment-for-advanced-hepatocellular-carcinoma","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/nivolumab-does-not-prolong-overall-survival-compared-with-sorafenib-in-first-line-treatment-for-advanced-hepatocellular-carcinoma\/","title":{"rendered":"Nivolumab Does Not Prolong Overall Survival Compared with Sorafenib In First-Line Treatment for Advanced Hepatocellular Carcinoma"},"content":{"rendered":"

In CheckMate 459 study nivolumab monotherapy did not significantly prolong overall survival (OS) compared with sorafenib as first-line treatment for patients with advanced hepatocellular carcinoma. However, nivolumab showed durable clinical activity in terms of response frequency and durability, with encouraging long-term survival, a differentiated and favourable safety profile with no new safety signals. The findings are published on 13 December 2021 in The Lancet Oncology<\/em> by Dr. Thomas Yau of the Department of Medicine, University of Hong Kong, Hong Kong SAR, China and colleagues.<\/p>\n

The authors commented that since the CheckMate 459 commenced, several studies have investigated PD1 or PD-L1 inhibitors alone or in combination with other drugs as first-line therapy for advanced hepatocellular carcinoma with atezolizumab plus bevacizumab being currently the standard of care in that setting. Until 2020, the only approved first-line therapies for advanced hepatocellular carcinoma included the multikinase inhibitors sorafenib and lenvatinib.  However, treatment with these drugs results in a high proportion of treatment-related adverse events (TRAEs) which often require dose interruption or reduction.<\/p>\n

Based on clinical activity of PD1 inhibitors in second-line treatment for advanced hepatocellular carcinoma, there is a strong rationale for their investigation in first-line setting. Single-agent nivolumab showed durable responses, manageable safety, and promising survival in patients with advanced hepatocellular carcinoma in the phase I\/II CheckMate 040 study.<\/p>\n

The confirmatory phase III CheckMate 459 study investigated nivolumab monotherapy compared with sorafenib monotherapy in patients with advanced hepatocellular carcinoma in the first-line setting. In this randomised, open-label, phase III study conducted in 22 countries, patients with no previous systemic therapy for advanced hepatocellular carcinoma with Child-Pugh class A and ECOG performance status score of 0 or 1, and regardless of viral hepatitis status were randomly assigned 1:1 to nivolumab or sorafenib until disease progression or unacceptable toxicity. The study primary endpoint was OS assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug.<\/p>\n

In total, 743 patients were randomly assigned, 371 to nivolumab and 372 to sorafenib. Median OS was 16.4 months (95% confidence interval [CI] 13.9\u201318.4) with nivolumab and 14.7 months (11.9\u201317.2) with sorafenib (hazard ratio 0.85, 95% CI 0.72\u20131.02; p = 0\u00b7075). However, the protocol-defined significance level of p = 0.0419 was not reached.<\/p>\n

The most common grade 3 or worse TRAEs were palmar-plantar erythrodysaesthesia (<1% in the nivolumab group versus 14% patients in the sorafenib group), aspartate aminotransferase increase (6% versus 4%), and hypertension (0 versus 7%). Serious TRAEs were reported in 12% patients receiving nivolumab and 11% patients receiving sorafenib. Four deaths in the nivolumab group and one death in the sorafenib group were treatment related.<\/p>\n

The study did not meet the prespecified boundary for significance for OS as the primary endpoint. However, improvement in response and sustained separation of the OS curves suggest a prolonged survival benefit with nivolumab at longer follow-up. Nivolumab had a manageable safety profile and no new safety signals were observed. The proportion of patients with grade 3\u20134 TRAEs and any-grade TRAEs leading to discontinuation was lower with nivolumab than with sorafenib.<\/p>\n

The authors commented that based on the results from CheckMate 459, nivolumab monotherapy is included in the NCCN Clinical Practice Guidelines in the US as a first-line systemic therapy option for patients with Child-Pugh score of A or B who are ineligible for anti-angiogenic drugs or tyrosine kinase inhibitors.<\/p>\n

The CheckMate 459 study was supported by Bristol Myers Squibb and Ono Pharmaceutical. The authors thanked Dako (an Agilent Technologies company) for collaborative development of the PD-L1 IHC 28-8 pharmDx assay.<\/p>\n

Reference<\/h4>\n

Yau T, Park J-W, Finn RS, et al.<\/em> Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial<\/a>. The<\/em> Lancet Oncology<\/em>; Published online 13 December 2021. DOI: https:\/\/doi.org\/10.1016\/S1470-2045(21)00604-5<\/a><\/p>\n

Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

In CheckMate 459 study nivolumab monotherapy did not significantly prolong overall survival (OS) compared with sorafenib as first-line treatment for patients with advanced hepatocellular carcinoma. However, nivolumab showed durable clinical activity in terms of response frequency and durability, with encouraging long-term survival, a differentiated and favourable safety profile with no new safety signals. The findings […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-27746","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27746","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=27746"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27746\/revisions"}],"predecessor-version":[{"id":45942,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27746\/revisions\/45942"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=27746"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=27746"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=27746"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}