1120P - Single center experience on patients with advanced melanoma treated with short-term anti-CTLA4 directly followed by anti-PD-1

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Melanoma and other Skin Tumours
Presenter Elisa. A. Rozeman
Citation Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379
Authors E..A. Rozeman1, A. Meerveld-Eggink1, F. Lalezari2, J.V. van Thienen1, J.B.A.G. Haanen1, C.U. Blank1
  • 1Department Of Medical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 2Department Of Radiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL



Combination of T-cell checkpoint blockade by anti-CTLA4 (ipilimumab, IPI) and anti-PD-1 (nivolumab, NIVO) is one of the most promising therapies in patients with late stage melanoma. It induces a superior objective response rate (ORR) (58%) as compared to single agent NIVO (44%) or IPI (19%) therapy (Checkmate 067 study). This superior efficacy is, however, associated with a high percentage of ≥ grade 3 adverse events (AEs)(55% versus 16% and 27%). The combination therapy is currently not available in the Netherlands, which prompted physicians to treat patients with short-term IPI directly followed by NIVO or pembrolizumab (PEM).


In this retrospective analysis, patients were included who were treated with short-term IPI q3wk (two courses day 0 and 21), directly followed by anti-PD-1 (starting at day 22 and onwards depending on the schedule (every 2 weeks for NIVO and 3 weeks for PEM)). Treatment related AEs data were collected from electronic patient dossiers and scored according to CTCAE 4.0 criteria. Response was evaluated using RECIST 1.1 for CT-scans and EORTC criteria for PET-scans.


Between May and December 2015, 40 patients with advanced melanoma were treated with IPI directly followed by anti-PD-1 (29/40 PEM, 11/40 NIVO). Baseline characteristics were: median age 54; male 55%; primary tumor site: skin 73%, mucosal 10%, unknown 17%; BRAFV600 mutation 58%; AJCC stage IV M1c 80%; brain metastases 20%; LDH >ULN 25%; prior systemic treatment 28%. Median follow-up (FU) so far is 31 weeks (range: 5-42 weeks) and an update will be presented. Treatment related grade ≥3 AEs occurred in 33% of patients; most prevalent were colitis (18%), increased ALT/AST (8%) and maculopapular rash (5%). In 6 patients (15%) treatment was permanently discontinued due to toxicity. ORR was 48% (95%CI: 32-64) and disease control rate was 75% (95%CI: 54-85). Ongoing responses were observed in 84% of responding patients.


Short-term IPI directly followed by NIVO/PEM seems to induce similar disease control as compared to concurrent IPI + NIVO, while grade 3/4 toxicity is lower. A randomized controlled clinical trial is in preparation to evaluate this alternative regimen.

Clinical trial identification

Legal entity responsible for the study

Netherlands Cancer Institute -Antoni van Leeuwenhoek hospital


Netherlands Cancer Institute -Antoni van Leeuwenhoek hospital


J.V. van Thienen: Advisory role: MSD and Bristol-Meyers-Squibb. J.B.A.G. Haanen: Research grants: MSD, Bristol-Myers-Squibb and GlaxoSmithKline. Advisory role: MSD Oncology, Pfizer, Bristol-Myers-Squibb, Novartis, Neon Therapeutics and Roche/Genentech. C. Blank: Research grant: Novartis. Advisory role: Novartis, Roche/Genentech, MSD, GlaxoSmithKline, Bristol-Myers-Squibb, Lilly and Pfizer. All other authors have declared no conflicts of interest.