Abstract 5005
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.
Clinical trial identification
Editorial acknowledgement
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.
Resources from the same session
2664 - Phase (Ph) II study of MBG453 + spartalizumab in patients (pts) with non-small cell lung cancer (NSCLC) and melanoma pretreated with anti–PD-1/L1 therapy
Presenter: Nicholas Mach
Session: Poster Display session 3
Resources:
Abstract
1285 - Preliminary results of STELLAR-001, a dose escalation phase I study of the anti-C5aR, IPH5401, in combination with durvalumab in advanced solid tumors.
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
3808 - GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
Presenter: Pierpaolo Correale
Session: Poster Display session 3
Resources:
Abstract
5677 - Immune correlates in peripheral blood samples in a preoperative window of opportunity randomized trial of nivolumab with or without tadalafil in resectable squamous cell carcinoma of the head and neck (SCCHN)
Presenter: Larry Harshyne
Session: Poster Display session 3
Resources:
Abstract
4854 - Phase 1 evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced malignancies
Presenter: John Powderly
Session: Poster Display session 3
Resources:
Abstract
4344 - Phase 1 Trial of CV301 in Combination with Anti-PD-1 Therapy in Non-squamous NSCLC
Presenter: Arun Rajan
Session: Poster Display session 3
Resources:
Abstract
4555 - Safety and efficacy results of the combination of DPX-Survivac, pembrolizumab and intermittent low dose cyclophosphamide (CPA) in subjects with advanced and metastatic solid tumors: preliminary results from the hepatocellular carcinoma (HCC), NSCLC, bladder cancer, & MSI-H cohorts
Presenter: Henry Conter
Session: Poster Display session 3
Resources:
Abstract
3012 - Excellent CBR and Prolonged PFS in Non-Squamous NSCLC with Oral CA-170, an Inhibitor of VISTA and PD-L1
Presenter: Vivek Radhakrishnan
Session: Poster Display session 3
Resources:
Abstract
2536 - Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers
Presenter: Christophe Le Tourneau
Session: Poster Display session 3
Resources:
Abstract
1845 - Induction of tumor-infiltrating functional CD8 positive cells and PD-L1 expression in esophageal cancer by S-588410
Presenter: Takashi Kojima
Session: Poster Display session 3
Resources:
Abstract