LAUSR

Abstract Background In phase III trials, the results of ipilimumab plus nivolumab combination therapy (IPI+NIVO) are promising for metastatic melanoma (MM), despite many treatment-related grade 3-4 adverse events (AEs). Here, we report real-world outcomes of IPI+NIVO for MM. Methods Patients with (non-uveal) MM who received 1st-line IPI+NIVO between 2015 and 2017 were selected from the Dutch Melanoma Treatment Registry, a nation-wide population based registry. Probability of 2nd-line treatment was estimated with competing risk analysis and overall survival (OS) with Kaplan-Meier method and Cox regression analysis. Results In total, 2116 pts with MM were treated with systemic therapy of which 151 pts with 1st-line IPI+NIVO. Median age was 58yrs versus 64yrs for pts treated with other systemic therapy in 1st-line. Half of the pts treated with 1st-line IPI+NIVO had elevated LDH, 90% an ECOG PS of ≤ 1, 32% brain metastases (21% symptomatic), 87% stage IV-M1c and 42% had BRAF-mutated melanoma. Grade 3-4 AEs occurred in 90 pts (60%); 39 (26%) had colitis, 37 (25%) hepatitis and 22 (13%) endocrine insufficiency. No deaths due to AEs were reported. For 66 pts who stopped IPI+NIVO because of AEs, 1-yr survival probability was 76% (95%CI: 66-87) compared to 57% (95%CI: 47-69) for the remaining 85 (56%) patients treated with 1st-line IPI+NIVO. A total of 50 (33%) pts completed all 4 courses of IPI+NIVO and 44 (29%) pts received maintenance with NIVO. The 1- and 2-yr OS probabilities (95%CI) were 66% (58-74%) and 55% (46-65%). Probability of still being in 1st-line IPI+NIVO at 1- and 2-yrs was 50% (95%CI; 42-59) and 34% (95%CI; 25-45). Cumulative incidence for 2nd-line treatment and death at 1yr were respectively 24% (95%CI: 18-33) and 27% (95%CI: 20-34). Adjusted HR for ECOG PS of ≥ 2, symptomatic brain metastases, liver metastases were respectively 3.1 (95%CI; 1.2-8.3), 2.0 (95%CI; 1.0-3.8), 2.2 (95%CI; 1.2-4.2). HR for BRAF-wildtype status was 0.5 (95%CI; 0.2-0.9). Conclusions Half of pts receiving 1st-line IPI+NIVO for MM had elevated LDH, one third brain metastases and a majority ECOG PS ≤ 1. Nevertheless, OS is encouraging especially in pts who stopped treatment due to AEs. With appropriate patient selection in real-world, promising results can be achieved with 1st-line IPI+NIVO. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure A.J.M. van den Eertwegh: Advisory / Consultancy: BMS; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen. A.C.J. van Akkooi: Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD - Merck; Advisory / Consultancy: MSD - Pfizer; Advisory / Consultancy: 4SC. J.W. de Groot: Advisory / Consultancy: BMS; Advisory / Consultancy: Merck. G.A.P. Hospers: Advisory / Consultancy: BMS; Advisory / Consultancy: Merck. E. Kapiteijn: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck. K.P.M. Suijkerbuijk: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Honoraria (institution): Roche. A.A.M. Van der Veldt: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Ipsen. J.B.A.G. Haanen: Advisory / Consultancy: Amgen; Advisory / Consultancy: AZ; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celsius Therapeutics; Advisory / Consultancy: GSK; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy, Research grant / Funding (institution): Neon Therapeutics; Advisory / Consultancy: AIMM; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Immunocore. All other authors have declared no conflicts of interest.