Improved progression-free survival in patients with advanced melanoma treated with relatlimab and nivolumab by Kassandra McFarlane, Samuel Chan +Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission. +1. Median progression-free survival is higher with combination treatment of relatlimab and nivolumab +2. Adverse events were more frequent in the combination treatment group +Evidence Rating Level: 1 (Excellent) Study Rundown: + +The activity and safety of relatlimab (LAG-3 inhibitor) and nivolumab (PD1 inhibitor) has not previously been assessed in patients with untreated advanced melanoma. This study explored the effect of this combination of immune checkpoint inhibitors on progression-free survival (PFS), safety, and overall survival in patients with advanced melanoma. The primary outcome was progression-free survival, while secondary outcomes included safety and overall survival (OS). 714 patients twelve years and older were randomly allocated in a 1:1 ratio to receive nivolumab with or without relatlimab (n = 355 and 359, respectively). Median PFS was longer at 10.1 months in the combination treatment group as compared to the nivolumab-only group at 4.6 months. Adverse events were more common in the combination treatment group as compared to the nivolumab-only group, and OS results have not matured. There were no significant differences between the groups for health-related quality of life measures. Limitations to this study include the absence of results for all outcomes (i.e., overall survival) as well as limited power to make concrete conclusions. Overall, this trial demonstrates that dual inhibition of LAG-3 and PD-1 is another therapeutic option for advanced melanoma. +Click to read the study in The New England Journal of Medicine +Click to read an accompanying editorial in The New England Journal of Medicine +Relevant Reading: CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma In-Depth [randomized controlled trial]: + +This phase 3 trial conducted at 111 sites around the world randomly allocated 714 patients aged 12 and older with advanced melanoma (either untreated metastatic or inoperable) to receive either nivolumab only (n = 359) or nivolumab and relatlimab (n = 355). The primary outcome was progression-free survival and it was found that the combination-treatment group had a median PFS of 10.1 months (95% confidence interval (CI), 6.4-15.7 months), whereas the nivolumab-only treatment group had a median PFS of 4.6 months (CI, 3.4 to 5.6 months) (hazard ratio (HR), 0.75; 95% CI, 0.62-0.92). At one year, PFS was 47.7% in the combination treatment group (95% CI, 41.8 to 53.2%) and 36.0% in the nivolumab-only group (95% CI, 30.5 to 41.6%). Safety and OS were secondary outcomes. The combination treatment group had a greater number of grade 3 or 4 adverse events (AEs) than the single treatment group (18.9% compared to 9.7%), but no new safety signals were seen in the combination treatment group. 14.6% of patients in the combination treatment group discontinued treatment due to AEs as compared to 6.7% of the nivolumab-only group. 0.8% of deaths in the combination treatment and 0.6% of deaths in the nivolumab-only group were considered treatment-related. OS has not matured at this time and will remain blinded. +©2022 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.