Abstract LB-055: Overall survival and safety experience from an expanded access program (EAP) of nivolumab (NIVO) for patients with advanced melanoma (MEL) who progressed after prior ipilimumab (IPI) treatment
Authors: Silva Milton Barros e , Schmerling Rafael , Melo Andreia Cristina de , Azevedo Sergio , Garicochea Bernardo , McWhirter Elaine , Smylie Michael , Gifoni Markus , Anjos Carlos Henrique dos , Petrella Teresa , Chacón Matias , Greco Martin , Nair Suresh , Avila Alexandre , Demelo Sheena , Jiang Joel , Ernst Scott 
Published: July 2017

Abstract
Background: NIVO (anti-PD-1) was initially approved in the USA as a second-line treatment for MEL based on the results of the phase III CheckMate 037 trial, which enrolled patients (pts) who progressed after prior IPI (anti-CTLA-4) therapy. The results of this trial showed a significantly improved tumor response with NIVO vs. chemotherapy; at a minimum follow-up of 2 years, grade 3/4 treatment-related adverse events (AEs) were reported in 14% of NIVO-treated pts. We report initial overall survival (OS) and safety data from an ongoing EAP of NIVO monotherapy in MEL pts who progressed on IPI therapy (CheckMate 168). Participating countries are Brazil, Canada, the USA, and Argentina.
Methods: In CheckMate 168 (NCT02142218), pts with stage III (unresectable) or stage IV MEL who progressed after prior IPI-containing therapy, with an ECOG performance status of 0 or 1, are eligible to receive NIVO 3 mg/kg Q2W for up to 24 months. Key exclusion criteria are active brain metastases, prior immune checkpoint inhibitor therapy other than anti-CTLA-4, and autoimmune disease. For the current analysis, the database lock occurred on November 1, 2016, and included 276 pts with at least 1 year of follow-up (total enrolled: 482).
Results: Among the 276 pts included in the current analysis, MEL subtypes were cutaneous (70%), mucosal (8%), acral (5%), uveal (5%), and other or missing (12%). More than half of the pts (55%) had M1c disease (13% with treated brain metastases and 42% without), and 41% had elevated lactate dehydrogenase levels at baseline. Pts had received 1 (21%), 2 (42%) or ≥3 (37%) prior systemic therapies for MEL, which included prior BRAF inhibitor therapy in 24% of pts (in addition to IPI). In the EAP, pts received a median of 8 NIVO doses (range: 1-48), with a median duration of therapy of 3.8 months (range: 0.03-22.1). Median OS in the 276 pts was 14.6 months (95% CI: 11.8-21.2), with a 1-year OS rate of 55.8% (95% CI: 49.2-61.8). Treatment-related AEs of any grade were reported in 69% of pts, most commonly fatigue (24%), diarrhea (17%), nausea (13%), and pruritus (12%), and led to discontinuation of NIVO in 8% of pts. Treatment-related AEs of grade 3/4 occurred in 15% of pts, and led to discontinuation of NIVO in 4% of pts. Any-grade serious AEs related to NIVO treatment were reported in 8% of pts. One death (0.4%) was attributed to study drug (toxic encephalopathy). For treatment-related AEs of potential immunologic origin, those of any grade occurred most commonly in the skin (33%), gastrointestinal tract (18%), and endocrine systems (14%).
Conclusions: The initial OS and safety experience from this EAP of NIVO after IPI therapy is consistent with clinical trial data, with no unexpected AEs. These findings suggest that NIVO clinical trial data can be generalized to the advanced melanoma population in a routine clinical practice setting.
Citation Format: Milton Barros e Silva, Rafael Schmerling, Andreia Cristina de Melo, Sergio Azevedo, Bernardo Garicochea, Elaine McWhirter, Michael Smylie, Markus Gifoni, Carlos Henrique dos Anjos, Teresa Petrella, Matias Chacón, Martin Greco, Suresh Nair, Alexandre Avila, Sheena Demelo, Joel Jiang, Scott Ernst. Overall survival and safety experience from an expanded access program (EAP) of nivolumab (NIVO) for patients with advanced melanoma (MEL) who progressed after prior ipilimumab (IPI) treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-055. doi:10.1158/1538-7445.AM2017-LB-055