{"id":26383,"date":"2020-09-19T18:00:00","date_gmt":"2020-09-19T18:00:00","guid":{"rendered":"http:\/\/9ca8ea7cc83dfe09570c67b4f38fc363"},"modified":"2024-11-03T15:16:18","modified_gmt":"2024-11-03T15:16:18","slug":"the-combination-of-nivolumab-and-cabozantinib-provides-a-new-first-line-treatment-option-in-advanced-clear-cell-rcc","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/the-combination-of-nivolumab-and-cabozantinib-provides-a-new-first-line-treatment-option-in-advanced-clear-cell-rcc\/","title":{"rendered":"The Combination of Nivolumab and Cabozantinib Provides a New First-Line Treatment Option in Advanced Clear Cell RCC"},"content":{"rendered":"

Efficacy data with nivolumab plus cabozantinib showing improved survival and response rates, together with an acceptable safety profile presented by Prof. Toni K. Choueiri of the Dana-Farber Cancer Institute and The Lank Centre for Genitourinary Oncology in Boston, USA at ESMO Virtual Congress 2020<\/a>, support this combination as a first-line treatment option for patients with advanced clear cell renal cell carcinoma (RCC).<\/p>\n

Prof. Choueiri presented first results from the phase III CheckMate 9ER study evaluating nivolumab plus cabozantinib compared with sunitinib as first-line treatment of advanced clear cell RCC. This study was prompted by reports that both nivolumab, a checkpoint inhibitor and cabozantinib, a tyrosine kinase inhibitor (TKI) administered as monotherapies demonstrated efficacy and a manageable safety profile in advanced RCC. Prof. Choueiri and colleagues reasoned that the immunomodulatory properties of cabozantinib may counteract tumour-induced immunosuppression.<\/p>\n

In CheckMate 9ER patients were stratified by IMDC risk score, tumour PD-L1 expression, as well as region and randomised 1:1 to receive a 240 mg flat dose of i.v. nivolumab every 2 weeks plus oral cabozantinib at 40 mg once daily or oral sunitinib at 50 mg for 4 weeks in 6-week cycles until disease progression or unacceptable toxicity occurred for a maximum treatment duration of two years.<\/p>\n

Progression-free survival (PFS; \u03b1 = 0.05 final) by blinded independent central review (BICR) served as the primary endpoint and secondary endpoints (hierarchical testing) included overall survival (OS; \u03b1 = 0.011 at the first interim analysis), objective response rate (ORR; \u03b1 = 0.05 at the final analysis) by BICR, and safety.<\/p>\n

Of the 651 patients randomised, 22.6% had favourable risk, 57.6% intermediate risk, and 19.7% of patients had poor risk and PD-L1 expression was \u22651% in 24.9% of patients.  A total of 323 patients were treated with the nivolumab plus cabozantinib combination and 328 patients received sunitinib.<\/p>\n

Nivolumab plus cabozantinib significantly improved survival over sunitinib<\/h4>\n

With median follow-up of 18.1 months and a minimum of 10.6 months, the study met all efficacy endpoints.<\/p>\n

The combination treatment doubled PFS over sunitinib; median PFS was 16.6 months compared to 8.3 months (hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.41\u20130.64], p < 0.0001).<\/p>\n

The OS was also significantly improved with nivolumab plus cabozantinib versus sunitinib, median OS was not reached (HR 0.60; 98.89% CI 0.40\u20130.89; p = 0.0010).<\/p>\n

The ORR was significantly higher at 55.7% (95% CI 50.1\u201361.2) with the combination versus 27.1% (95% CI 22.4\u201332.3) with sunitinib (p < 0.0001); the median duration of response was 20.2 versus 11.5 months, respectively. With nivolumab plus cabozantinib 8.0% of patients achieved complete response compared with 4.6% of sunitinib patients.<\/p>\n

These favourable results were consistent across prespecified IMDC risk and PD-L1 subgroups.<\/p>\n

Any-grade treatment-related adverse events (TRAEs) occurred in 96.6% of patients receiving the combination compared with 93.1% of patients on sunitinib and grade \u22653 TRAEs were reported in 60.6% versus 50.9% of patients, respectively. <\/p>\n

TRAEs led to discontinuation of nivolumab in 5.6% of patients, and of cabozantinib in 6.6% of patients whereas 3.1% of patients discontinued the combination (total 15.3%) and 8.8% of patients discontinued sunitinib.<\/p>\n

One treatment-related death occurred with nivolumab plus cabozantinib and two occurred with sunitinib. <\/p>\n

Health-related Quality-of-life also favoured the combination treatment.<\/p>\n

Conclusions<\/h4>\n

Based on these favourable results, the authors concluded that nivolumab plus cabozantinib demonstrated PFS, OS and ORR that were superior to sunitinib in the first-line treatment for advanced clear cell RCC.<\/p>\n

Taken together with a safety profile for the combination that was manageable and consistent with the known single-agent adverse event profiles of nivolumab and cabozantinib, these efficacy results support nivolumab cabozantinib as a new checkpoint inhibitor plus TKI option for patients with advanced clear cell RCC.<\/p>\n

Funding for this study was reported from Bristol-Myers Squibb Company (Princeton, NJ), ONO Pharmaceutical Company Ltd. (Osaka, Japan), and Exelixis Inc. (Alameda, CA).<\/p>\n

Reference<\/h4>\n

696O_PR \u2013 Choueiri TK, Powles <\/sup>T, Burotto M, et al.<\/em> Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: First results from the randomized phase III CheckMate 9ER trial. ESMO Virtual Congress 2020<\/a>.<\/p>\n

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

Efficacy data with nivolumab plus cabozantinib showing improved survival and response rates, together with an acceptable safety profile presented by Prof. Toni K. Choueiri of the Dana-Farber Cancer Institute and The Lank Centre for Genitourinary Oncology in Boston, USA at ESMO Virtual Congress 2020, support this combination as a first-line treatment option for patients with […]<\/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-26383","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26383","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=26383"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26383\/revisions"}],"predecessor-version":[{"id":45556,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26383\/revisions\/45556"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=26383"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=26383"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=26383"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}