1106P International experience of ipilimumab and nivolumab in patients with advanced melanoma

Abstract

Background: Immune checkpoint inhibition (ICI) combination therapy with ipilimumab (IPI) and nivolumab (NIVO), considered a standard of care for metastatic melanoma, has shown high rates of objective response rate (ORR), progression free survival (PFS) and overall survival (OS), but at a cost of significant toxicity. We aimed to analyse the efficacy and toxicity outcomes related to treatment with IPI and NIVO in routine practice in a multicentre cohort of patients (pts) with metastatic melanoma. Methods: We conducted a retrospective review of medical notes of pts with advanced melanoma (unresectable Stage 3 or Stage 4) treated with IPI and NIVO between 2015 and 2020 at 6 centers across Europe, USA and Australia. Baseline characteristics were collected including the presence of brain metastases (BM). The primary endpoint was OS in the non-BM cohort. Secondary endpoints were PFS, ORR and immune-related adverse events (irAE) in the whole cohort and BM pts only. Results: 696 pts with median follow-up of 13 months (m) were included. Median age was 58 years, 400 (57%) were male, 678 (97%) had PS- ECOG 0-1. Primary site was cutaneous in 487 pts (70%), unknown in 133 pts (20%) and other (acral, mucosal and uveal) in 77 pts (10%). 352 pts (50.5%) had a BRAF mutation, 516 pts (74%) were treatment naive, 241 pts (35%) had BM, of which 131 (18%) were untreated. 277 pts (40%) had elevated LDH. ORR was 48% (95% CI, 45-52). Median PFS (mPFS) was 6m (95% CI, 4.3-7.6), median OS (mOS) was 38m (95% CI, 26.6-49.3) for the entire cohort. mOS in non-BM pts was 52 m (95% CI, NR-NR) and 14m (95% 5-23) in BM pts. Intracranial (IC) ORR was 43% (95% CI, 37-49) and IC disease-control-rate was 56% (95% CI, 49-62). 253 pts (36%) started maintenance NIVO. Any irAE occurred in 76% of pts; grade 3/4 in 44%, hospital admission rate was 36%, and 4 (0.7%) treatment-related deaths (1 pneumonitis, 2 myocarditis and 1 colitis) were recorded. Conclusions: The findings on this large cohort of pts support efficacy and provide insights into pts characteristics and outcomes associated with IPI and NIVO treatment for a heterogeneous population with advanced melanoma and are comparable with those of previously reported pivotal trial, Checkmate 067. Further analysis of the data including prognostic factors is ongoing. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: N. Cook: Advisory/Consultancy, scientific advisory board: Redx Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution), scientific advisory board: Tarveda Pharmaceuticals; Advisory/Consultancy, scientific advisory board: Neomed pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution), scientific advisory board: Roche Pharmaceuticals; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Redx; Research grant/Funding (institution): Astrazeneca; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): UCB; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Milenium; Research grant/Funding (institution): Starpharma; Research grant/Funding (institution): Orion; Non-remunerated activity/ies, scientific advisory board: Roche; Leadership role: Experimental Cancer Medicine Centre (ECMC) Strategy group, UK. D.M. Graham: Honoraria (self): Clinigen; Honoraria (self): McCann Health; Research grant/Funding (institution): Pfizer. A. Gupta: Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy: Amgen; Non-remunerated activity/ies: Member of the NCRI Skin Clinical Studies Group; Non-remunerated activity/ies: Member of the Association of Cancer Physicians. A.M. Arance Fernandez: Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck. D.B. Johnson: Advisory/Consultancy: Array Biopharma; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy: Jansen; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Research grant/Funding (self): Incyte; Non-remunerated activity/ies: ASCO Melanoma Scientific Committee Chair; Non-remunerated activity/ies: NCCN Melanoma Committee. G.V. Long: Advisory/Consultancy: Aduro; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol- Myers Squibb; Advisory/Consultancy: Mass-Array; Advisory/Consultancy: Merck; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: OncoSec Medical; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Roche; Advisory/Consultancy: QBiotics; Advisory/Consultancy: Sandoz; Leadership role: President, Society for Melanoma Research; Leadership role: Australian Practice Guidelines Steering Committee. L. Pickering: Advisory/Consultancy: Astellas; Advisory/Consultancy: AZ; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Advisory/Consultancy: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony: EUSA; Advisory/Consultancy, Speaker Bureau/Expert testimony: GSK; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Immunocore; Research grant/Funding (institution): Pharmacyclics; Research grant/Funding (institution): Aveo; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Achilles; Leadership role: UK Clinical Studies Group for Renal and Bladder Cancer; Leadership role: UK Clinical Reference Group for Chemotherapy; Non-remunerated activity/ies: Member of Association of Cancer Physicians (UK); Non-remunerated activity/ies: Member and Fellow of Royal College of Physicians (UK); Non-remunerated activity/ies: Member of British Uro-Oncology Group. J. Larkin: Advisory/Consultancy: Achilles; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boston Biomedical; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Eisai; Advisory/Consultancy: EUSA Pharma; Advisory/Consultancy: GSK; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Imugene; Advisory/Consultancy: Incyte; Advisory/Consultancy: iOnctura; Advisory/Consultancy: Kymab; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: MSD; Advisory/Consultancy: Nektar; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Secarna; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Immunocore; Research grant/Funding (institution): Pharmacyclics; Research grant/Funding (institution): Aveo; Research grant/Funding (institution): Nektar Therapeutics; Research grant/Funding (institution): Merck, Sharp & Dohme Limited (MSD); Research grant/Funding (institution): Achilles Therapeutics. C.U. Blank: Honoraria (institution), Research grant/Funding (institution): BMS; Honoraria (institution): MSD; Honoraria (institution): Roche; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution): GSK; Honoraria (institution): AZ; Honoraria (institution): Pfizer; Honoraria (institution): Lilly; Honoraria (institution): Genmab; Honoraria (institution): Pierre Fabre; Honoraria (self): Third Rock Ventures; Shareholder/Stockholder/Stock options: Uniti Cars; Shareholder/Stockholder/Stock options: Immagene B.V.; Research grant/Funding (institution): NanoString. P. Lorigan: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy: Amgen; Non-remunerated activity/ies: Roche; Advisory/Consultancy: Neracare/Melagenix. All other authors have declared no conflicts of interest.