PMID- 28158487
OWN - NLM
STAT- MEDLINE
DCOM- 20170502
LR  - 20200206
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 28
IP  - 4
DP  - 2017 Apr 1
TI  - Short-term CTLA-4 blockade directly followed by PD-1 blockade in advanced 
      melanoma patients: a single-center experience.
PG  - 862-867
LID - 10.1093/annonc/mdw692 [doi]
AB  - BACKGROUND: Combination of T cell checkpoint blockade by CTLA-4- and 
      PD-1-blockade is one of the most promising therapies in patients with advanced 
      melanoma. It induces superior response rates when compared with single-agent 
      therapy, but at the cost of a high percentage of grade 3 and 4 adverse events 
      (AEs). This combination therapy was until July 2016 not available in the 
      Netherlands, which prompted several physicians to treat patients with less than 
      standard numbers of courses of ipilimumab followed directly by nivolumab or 
      pembrolizumab. PATIENTS AND METHODS: In this retrospective analysis, patients 
      were included who were treated with two courses (day 0 and 21) anti-CTLA-4 
      (ipilimumab 3 mg/kg q3wk), directly followed by anti-PD-1 (starting at day 22 
      with nivolumab 3mg/kg q2wk or pembrolizumab 2 mg/kg q3wk). Data on 
      treatment-related AEs were collected from electronic patient records and scored 
      according to CTCAE 4.03 criteria. Overall response was evaluated using RECIST 1.1 
      for CT-scans and EORTC criteria for PET-scans. RESULTS: Forty advanced melanoma 
      patients could be included (29/40 pembrolizumab, 11/40 nivolumab). Median 
      follow-up (FU) was 51 weeks (range: 4-63 weeks) with a minimum FU of 26 weeks. 
      Treatment-related AEs of grade 3 and 4 occurred in 38% of the patients. The best 
      overall response rate (BORR) was 55% (95% CI 39-70) and disease control rate was 
      75% (95% CI 59-87). Ongoing responses were observed in 82% of responding 
      patients. CONCLUSION: Treatment with short-term CTLA-4 blockade directly followed 
      by PD-1 blockade may have similar efficacy but potentially lower toxicity when 
      compared with concurrent therapy with anti-CTLA-4 and anti-PD-1. These results 
      warrant further investigation in a prospective randomized controlled clinical 
      trial.
CI  - (c) The Author 2017. Published by Oxford University Press on behalf of the European 
      Society for Medical Oncology. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Meerveld-Eggink, A
AU  - Meerveld-Eggink A
AD  - Department of Medical Oncology, Antoni van Leeuwenhoek, Amsterdam, The 
      Netherlands.
FAU - Rozeman, E A
AU  - Rozeman EA
AD  - Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The 
      Netherlands.
FAU - Lalezari, F
AU  - Lalezari F
AD  - Division of Radiology, The Netherlands Cancer Institute, Amsterdam, The 
      Netherlands.
FAU - van Thienen, J V
AU  - van Thienen JV
AD  - Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The 
      Netherlands.
FAU - Haanen, J B A G
AU  - Haanen JBAG
AD  - Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The 
      Netherlands.
FAU - Blank, C U
AU  - Blank CU
AD  - Department of Immunology, Netherlands Cancer Institute, Plesmanlaan, Amsterdam, 
      The Netherlands.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Ipilimumab)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 31YO63LBSN (Nivolumab)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - CTLA-4 Antigen/antagonists & inhibitors
MH  - Female
MH  - Humans
MH  - Ipilimumab
MH  - Male
MH  - Melanoma/*drug therapy
MH  - Middle Aged
MH  - Nivolumab
MH  - Programmed Cell Death 1 Receptor/antagonists & inhibitors
MH  - Retrospective Studies
MH  - Treatment Outcome
OTO - NOTNLM
OT  - CTLA-4 blockade
OT  - PD-1 blockade
OT  - checkpoint inhibition
OT  - combination therapy
OT  - melanoma
EDAT- 2017/02/06 06:00
MHDA- 2017/05/04 06:00
CRDT- 2017/02/04 06:00
PHST- 2016/08/05 00:00 [received]
PHST- 2017/02/06 06:00 [pubmed]
PHST- 2017/05/04 06:00 [medline]
PHST- 2017/02/04 06:00 [entrez]
AID - S0923-7534(19)32062-9 [pii]
AID - 10.1093/annonc/mdw692 [doi]
PST - ppublish
SO  - Ann Oncol. 2017 Apr 1;28(4):862-867. doi: 10.1093/annonc/mdw692.