{"id":27557,"date":"2021-10-20T09:36:00","date_gmt":"2021-10-20T09:36:00","guid":{"rendered":"http:\/\/38f25f4d2047314e98d1cd265d4c4b5c"},"modified":"2024-11-03T15:14:12","modified_gmt":"2024-11-03T15:14:12","slug":"nivolumab-plus-low-dose-ipilimumab-demonstrates-clinical-benefit-in-first-line-treatment-for-msi-h-dmmr-mcrc","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/nivolumab-plus-low-dose-ipilimumab-demonstrates-clinical-benefit-in-first-line-treatment-for-msi-h-dmmr-mcrc\/","title":{"rendered":"Nivolumab Plus Low-Dose Ipilimumab Demonstrates Clinical Benefit in First-Line Treatment for MSI-H\/dMMR mCRC"},"content":{"rendered":"

Durable and deep tumour responses were observed in patients with microsatellite instability-high\/mismatch repair-deficient (MSI-H\/dMMR) metastatic colorectal cancer (mCRC) treated with first-line nivolumab plus low-dose ipilimumab, regardless of baseline demographic and tumour characteristics, including BRAF<\/em> or KRAS<\/em> mutation status. Median duration of response (DoR), progression-free survival (PFS), and overall survival (OS) were not reached, with a minimum follow-up of 24.2 months. This combination therapy was well tolerated at a median follow-up of 29.0 months. The findings from the CheckMate 142 study are published by Prof. Heinz-Josef Lenz of the USC Norris Comprehensive Cancer Center in Los Angeles, CA, USA and colleagues on 12 October 2021 in the Journal of Clinical Oncology<\/em>.<\/p>\n

CheckMate 142 is a phase II, multicohort, non-randomised study of nivolumab-based therapies in patients with previously treated and untreated MSI-H and non\u2013MSI-H mCRC. In patients with MSI-H\/dMMR mCRC who had one or more prior treatments (second-line or greater), nivolumab monotherapy and nivolumab plus low-dose ipilimumab followed by nivolumab monotherapy demonstrated promising clinical activity as reflected by high and durable responses after a median follow-up of 12.0 and 13.4 months, respectively. Nivolumab monotherapy was well tolerated, and nivolumab plus low-dose ipilimumab had a manageable safety profile.<\/p>\n

Based on these results, nivolumab received accelerated US Food and Drug Administration approval as a single agent or in combination with ipilimumab for patients with MSI-H\/dMMR mCRC that progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.<\/p>\n

An indirect comparison of CheckMate 142 cohorts suggested that nivolumab plus low-dose ipilimumab demonstrated improved clinical benefit relative to nivolumab monotherapy, with a favourable benefit-risk profile, in second-line or greater MSI-H\/dMMR mCRC.<\/p>\n

The study team now reports the results of nivolumab plus low-dose ipilimumab as first-line therapy for patients with MSI-H\/dMMR mCRC. This is the first report of a dual immune checkpoint inhibitors combination treatment in first-line MSI-H\/dMMR mCRC.<\/p>\n

Patients with no prior treatment in the metastatic setting for MSI-H\/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary endpoint was objective response rate (ORR) per investigator assessment (RECIST v1.1).<\/p>\n

Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. The ORR was 69% (95% confidence interval [CI] 53 to 82) and disease control rate was 84% (95% CI 70.5 to 93.5) with 13% complete response rate. Median DoR was not reached; 74% of responders had ongoing responses at data cut-off.<\/p>\n

Median PFS and median OS were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumour characteristics, including BRAF<\/em> or KRAS<\/em> mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free.<\/p>\n

Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events.<\/p>\n

The authors commented that the limitations of their study include its non-randomised design, the absence of a standard-of-care or anti\u2013PD1 monoclonal antibody monotherapy comparator arm, and its small sample size.<\/p>\n

The authors concluded that nivolumab plus low-dose ipilimumab demonstrated robust, deep, and durable clinical benefit as a first-line treatment for patients with MSI-H\/dMMR mCRC. This combination represents a first-line treatment option for MSI-H\/dMMR mCRC with potential for improved efficacy relative to anti-PD1 monotherapy and conventional chemotherapy with or without targeted therapy. A confirmatory randomised phase III study, CheckMate 8HW, is underway.<\/p>\n

The findings were presented in part at the ASCO 2020 Annual Meeting and the ASCO 2021 Gastrointestinal Cancers Symposium.<\/p>\n

The study was supported by Bristol Myers Squibb.<\/p>\n

Reference<\/h4>\n

Lenz H-J, Van Cutsem E, Limon ML, et al.<\/em> First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High\/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study<\/a>. JCO<\/em>; Published online 12 October 2021. DOI: 10.1200\/JCO.21.01015<\/p>\n

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

Durable and deep tumour responses were observed in patients with microsatellite instability-high\/mismatch repair-deficient (MSI-H\/dMMR) metastatic colorectal cancer (mCRC) treated with first-line nivolumab plus low-dose ipilimumab, regardless of baseline demographic and tumour characteristics, including BRAF or KRAS mutation status. Median duration of response (DoR), progression-free survival (PFS), and overall survival (OS) were not reached, with a […]<\/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-27557","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27557","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=27557"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27557\/revisions"}],"predecessor-version":[{"id":45127,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27557\/revisions\/45127"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=27557"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=27557"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=27557"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}