PMID- 38493679
OWN - NLM
STAT- Publisher
LR  - 20240410
IS  - 1532-2157 (Electronic)
IS  - 0748-7983 (Linking)
VI  - 50
IP  - 6
DP  - 2024 Mar 12
TI  - The effect of a single dose of nivolumab prior to isolated limb perfusion for 
      patients with in-transit melanoma metastases: An interim analysis of a phase 
      Ib/II randomized double-blind placebo-controlled trial (NivoILP trial).
PG  - 108265
LID - S0748-7983(24)00317-2 [pii]
LID - 10.1016/j.ejso.2024.108265 [doi]
AB  - OBJECTIVE: ILP has shown to achieve high response rates in patients with melanoma 
      ITM. Possibly there is a synergistic mechanism of action of ILP and anti-PD1. The 
      aim of this trial was to investigate the safety and efficacy of adding a single 
      dose of systemic anti-PD1 to isolated limb perfusion (ILP) for patients with 
      melanoma in-transit metastases (ITM). METHODS: In this placebo controlled 
      double-blind phase Ib/II trial, patients with melanoma ITM were randomized 1:1 to 
      either a single systemic dose of nivolumab or placebo one day prior to ILP. The 
      primary endpoint was complete response (CR) rate at three months, and safety in 
      terms of incidence and severity of adverse events (AEs). RESULTS: A total of 20 
      patients were included. AEs of any grade occurred in 90% of patients in the 
      nivolumab arm and in 80% in the placebo arm within three months after ILP. Grade 
      3 AEs were reported in 40% and 30% respectively, most commonly related to wound 
      infection, wound dehiscence, or skin necrosis. There were no grade 4 or 5 AEs 
      reported. The CR rate was 75% in the nivolumab arm and 60% in the placebo arm. 
      The 1-year local progression-free rate was 86% in the nivolumab arm and 67% in 
      the placebo arm. The 1-year OS was 100% in both arms. CONCLUSION: For patients 
      with melanoma ITM, the addition of a single systemic dose of nivolumab the day 
      before ILP is considered safe and feasible with promising efficacy. Accrual will 
      continue in a phase 2 trial.
CI  - (c) 2024 Published by Elsevier Ltd.
FAU - Holmberg, Carl-Jacob
AU  - Holmberg CJ
AD  - Sahlgrenska University Hospital, Department of Surgery, Gothenburg, Sweden; 
      Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of 
      Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 
      Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of 
      Gothenburg, Gothenburg, Sweden.
FAU - Zijlker, Lisanne P
AU  - Zijlker LP
AD  - The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the 
      Netherlands; Melanoma Institute Australia, Sydney, New South Wales, Australia.
FAU - Katsarelias, Dimitrios
AU  - Katsarelias D
AD  - Sahlgrenska University Hospital, Department of Surgery, Gothenburg, Sweden; 
      Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of 
      Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 
      Sweden.
FAU - Huibers, Anne E
AU  - Huibers AE
AD  - Sahlgrenska University Hospital, Department of Surgery, Gothenburg, Sweden; 
      Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of 
      Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 
      Sweden.
FAU - Wouters, Michel W J M
AU  - Wouters MWJM
AD  - The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the 
      Netherlands.
FAU - Schrage, Yvonne
AU  - Schrage Y
AD  - The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the 
      Netherlands.
FAU - Reijers, Sophie J M
AU  - Reijers SJM
AD  - The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the 
      Netherlands.
FAU - van Thienen, Johannes V
AU  - van Thienen JV
AD  - The Netherlands Cancer Institute, Department of Medical Oncology, Amsterdam, the 
      Netherlands.
FAU - Grunhagen, Dirk J
AU  - Grunhagen DJ
AD  - Erasmus Medical Center, Department of Surgical Oncology, Rotterdam, the 
      Netherlands.
FAU - Martner, Anna
AU  - Martner A
AD  - TIMM Laboratory, Sahlgrenska Center for Cancer Research, Department of 
      Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, 
      University of Gothenburg, Gothenburg, Sweden.
FAU - Nilsson, Jonas A
AU  - Nilsson JA
AD  - Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of 
      Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 
      Sweden; Harry Perkins Institute of Medical Research, University of Western 
      Australia, Perth, Western Australia, Australia.
FAU - van Akkooi, Alexander C J
AU  - van Akkooi ACJ
AD  - Melanoma Institute Australia, Sydney, New South Wales, Australia; Faculty of 
      Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of 
      Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, 
      Australia.
FAU - Ny, Lars
AU  - Ny L
AD  - Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; 
      Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, 
      University of Gothenburg, Gothenburg, Sweden.
FAU - van Houdt, Winan J
AU  - van Houdt WJ
AD  - The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the 
      Netherlands.
FAU - Olofsson Bagge, Roger
AU  - Olofsson Bagge R
AD  - Sahlgrenska University Hospital, Department of Surgery, Gothenburg, Sweden; 
      Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of 
      Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 
      Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of 
      Gothenburg, Gothenburg, Sweden. Electronic address: roger.olofsson.bagge@gu.se.
LA  - eng
PT  - Journal Article
DEP - 20240312
PL  - England
TA  - Eur J Surg Oncol
JT  - European journal of surgical oncology : the journal of the European Society of 
      Surgical Oncology and the British Association of Surgical Oncology
JID - 8504356
SB  - IM
OTO - NOTNLM
OT  - Anti-PD1
OT  - In-transit metastases
OT  - Isolated limb perfusion
OT  - Melanoma
COIS- Declaration of competing interest ACJvA is a member of the Advisory Board for, 
      and received consultancy honoraria from, Amgen, Bristol-Myers Squibb, Neracare, 
      Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Provectus, Sanofi, Sirius 
      Medical, and 4SC. WvH has received institutional honoraria, speakers honorarium, 
      or institutional research grants from Amgen, Bristol-Myers Squibb, Novartis, 
      MSD-Merck, Belpharma, Sanofi and Sirius Medical. ROB has received institutional 
      research grants from Bristol-Myers Squibb (BMS) and SkyLineDx, speaker honorarium 
      from Roche and Pfizer and has served on advisory boards for Amgen, BD/BARD, 
      Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Roche and Sanofi 
      Genzyme. Remaining authors have no conflicts of interest to declare.
EDAT- 2024/03/18 00:42
MHDA- 2024/03/18 00:42
CRDT- 2024/03/17 19:10
PHST- 2024/01/18 00:00 [received]
PHST- 2024/03/05 00:00 [revised]
PHST- 2024/03/10 00:00 [accepted]
PHST- 2024/03/18 00:42 [medline]
PHST- 2024/03/18 00:42 [pubmed]
PHST- 2024/03/17 19:10 [entrez]
AID - S0748-7983(24)00317-2 [pii]
AID - 10.1016/j.ejso.2024.108265 [doi]
PST - aheadofprint
SO  - Eur J Surg Oncol. 2024 Mar 12;50(6):108265. doi: 10.1016/j.ejso.2024.108265.