PMID- 32503946
OWN - NLM
STAT- MEDLINE
DCOM- 20210521
LR  - 20210521
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 8
IP  - 1
DP  - 2020 Jun
TI  - Overall survival at 5 years of follow-up in a phase III trial comparing 
      ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma.
LID - 10.1136/jitc-2019-000391 [doi]
LID - e000391
AB  - BACKGROUND: We have previously reported significantly longer overall survival 
      (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced 
      melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This 
      follow-up analysis reports a 5-year update of OS and safety. METHODS: This 
      randomized, multicenter, double-blind, phase III trial included patients with 
      untreated or previously treated unresectable stage III or IV melanoma. Patients 
      were randomly assigned (1:1) to ipilimumab 10 mg/kg or 3 mg/kg every 3 weeks for 
      4 doses. The primary end point was OS. RESULTS: At a minimum follow-up of 61 
      months, median OS was 15.7 months (95% CI 11.6 to 17.8) at 10 mg/kg and 11.5 
      months (95% CI 9.9 to 13.3) at 3 mg/kg (HR 0.84, 95% CI 0.71 to 0.99; p=0.04). In 
      a subgroup analysis, median OS of patients with asymptomatic brain metastasis was 
      7.0 months (95% CI 4.0 to 12.8) in the 10 mg/kg group and 5.7 months (95% CI 4.2 
      to 7.0) in the 3 mg/kg group. In patients with wild-type or mutant BRAF tumors, 
      median OS was 13.8 months (95% CI 10.2 to 17.0) and 33.2 months (95% CI 19.4 to 
      45.2) in the 10 mg/kg group, and 11.2 months (95% CI 9.2 to 13.8) and 19.7 months 
      (95% CI 11.6 to 25.3) in the 3 mg/kg group, respectively. The incidence of grade 
      3/4 treatment-related AEs was 36% in the 10 mg/kg group vs 20% in the 3 mg/kg 
      group, and deaths due to treatment-related AEs occurred in four (1%) and two 
      patients (1%), respectively. CONCLUSIONS: This 61-month follow-up of a phase III 
      trial showed sustained long-term survival in patients with advanced melanoma who 
      started metastatic treatment with ipilimumab monotherapy, and confirmed the 
      significant benefit for those who received ipilimumab 10 mg/kg vs 3 mg/kg. These 
      results suggest the emergence of a plateau in the OS curve, consistent with 
      previous ipilimumab studies. TRIAL REGISTRATION NUMBER: NCT01515189.
CI  - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published 
      by BMJ.
FAU - Ascierto, Paolo Antonio
AU  - Ascierto PA
AUID- ORCID: 0000-0002-8322-475X
AD  - Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale 
      Tumori IRCCS Fondazione Pascale, Napoli, Italy paolo.ascierto@gmail.com.
FAU - Del Vecchio, Michele
AU  - Del Vecchio M
AD  - Unit of Melanoma Medical Oncology, Fondazione IRCCS Istituto Nazionale dei 
      Tumori, Milano, Lombardia, Italy.
FAU - Mackiewicz, Andrzej
AU  - Mackiewicz A
AD  - Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Center, 
      Poznan Medical University, Poznan, Poland.
FAU - Robert, Caroline
AU  - Robert C
AD  - Department of Medicine, Dermatology Service, Gustave Roussy, Villejuif and 
      Paris-Sud-University, Le Kremlin-Bicetre, France.
FAU - Chiarion-Sileni, Vanna
AU  - Chiarion-Sileni V
AD  - Melanoma Oncology Unit, Istituto Oncologico Veneto-IRCCS, Padova, Italy.
FAU - Arance, Ana
AU  - Arance A
AD  - Hospital Clinic and Institut D'Investigacions Biomediques August Pi i Sunyer, 
      Barcelona, Spain.
FAU - Lebbe, Celeste
AU  - Lebbe C
AD  - Universite de Paris, INSERM, Dermatology and CIC, Saint Louis Hospital, Paris, 
      France.
FAU - Svane, Inge Marie
AU  - Svane IM
AD  - Center for Cancer Immune Therapy, Herlev Hospital, Herlev, Denmark.
AD  - Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
FAU - McNeil, Catriona
AU  - McNeil C
AD  - Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, New South 
      Wales, Australia.
FAU - Rutkowski, Piotr
AU  - Rutkowski P
AUID- ORCID: 0000-0002-8920-5429
AD  - Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie 
      Institute-Oncology Center, Warsaw, Poland.
FAU - Loquai, Carmen
AU  - Loquai C
AD  - Department of Dermatology, University Medical Center, Mainz, Germany.
FAU - Mortier, Laurent
AU  - Mortier L
AD  - Clinique de Dermatologie, Unite d'Onco-Dermatologie, INSERM U1189, Centre 
      Hospitalier Regional Universitaire de Lille, Hopital Claude Huriez, Lille, 
      France.
FAU - Hamid, Omid
AU  - Hamid O
AD  - Melanoma Center, The Angeles Clinic and Research Institute, Los Angeles, 
      California, USA.
FAU - Bastholt, Lars
AU  - Bastholt L
AD  - Department of Oncology, Odense University Hospital, Odense, Denmark.
FAU - Dreno, Brigitte
AU  - Dreno B
AD  - Department of Oncodermatology, University Hospital Centre Nantes, Nantes, Pays de 
      la Loire, France.
FAU - Schadendorf, Dirk
AU  - Schadendorf D
AD  - Department of Dermatology, University Hospital Essen, Essen, Nordrhein-Westfalen, 
      Germany.
AD  - Department of Dermatology, German Cancer Consortium, Heidelberg, Germany.
FAU - Garbe, Claus
AU  - Garbe C
AD  - Department of Dermatology, Eberhard Karls Universitat Tubingen, Tubingen, 
      Baden-Wurttemberg, Germany.
FAU - Nyakas, Marta
AU  - Nyakas M
AD  - Department of Oncology, Oslo University Hospital, Oslo, Norway.
FAU - Grob, Jean-Jacques
AU  - Grob JJ
AD  - Dermatology and Skin Cancers Department, Aix-Marseille University, APHM, 
      Marseille, France.
FAU - Thomas, Luc
AU  - Thomas L
AD  - Department of Dermatology, Centre Hospitalier Lyon-Sud, Pierre-Benite, France.
FAU - Liszkay, Gabriella
AU  - Liszkay G
AD  - Department of Oncodermatology, National Institute of Oncology, Budapest, Hungary.
FAU - Smylie, Michael
AU  - Smylie M
AD  - Department of Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
FAU - Hoeller, Christoph
AU  - Hoeller C
AD  - Division of General Dermatology and Dermato-Oncology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Ferraresi, Virginia
AU  - Ferraresi V
AD  - Unit of Medical Oncology, IRCCS-Regina Elena National Cancer Institute, Rome, 
      Italy.
FAU - Grange, Florent
AU  - Grange F
AD  - Department of Dermatology, University Hospital Centre Reims, Reims, 
      Champagne-Ardenne, France.
FAU - Gutzmer, Ralf
AU  - Gutzmer R
AD  - Operative Dermatology and Dermato-Oncology, Medizinische Hochschule Hannover, 
      Hannover, Niedersachsen, Germany.
FAU - Pikiel, Joanna
AU  - Pikiel J
AD  - Department of Oncology, Wojewodzkie Centrum Oncologii, Gdansk, Poland.
FAU - Hosein, Fareeda
AU  - Hosein F
AD  - Oncology Clinical Development, Bristol-Myers Squibb Co, Princeton, New Jersey, 
      USA.
FAU - Simsek, Burcin
AU  - Simsek B
AD  - Oncology Clinical Development, Bristol-Myers Squibb Co, Princeton, New Jersey, 
      USA.
AD  - Department of Biostatistics, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
FAU - Maio, Michele
AU  - Maio M
AD  - Center for Immuno-Oncology, University Hospital of Siena, Instituto Toscano 
      Tumori, Siena, Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT01515189
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (Ipilimumab)
SB  - IM
EIN - J Immunother Cancer. 2020 Jul;8(2):. PMID: 32661117
MH  - Adult
MH  - Aged
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology/immunology
MH  - Follow-Up Studies
MH  - Humans
MH  - Immune Checkpoint Inhibitors/*administration & dosage/adverse effects
MH  - Incidence
MH  - Ipilimumab/*administration & dosage/adverse effects
MH  - Melanoma/*drug therapy/immunology/mortality/pathology
MH  - Middle Aged
MH  - Progression-Free Survival
MH  - Skin Neoplasms/*drug therapy/immunology/mortality/pathology
MH  - Survival Rate
MH  - Young Adult
PMC - PMC7279645
OTO - NOTNLM
OT  - immunology
OT  - oncology
OT  - randomized trials
COIS- Competing interests: PAA has served as a consultant to Bristol-Myers Squibb, 
      Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre 
      Fabre, Incyte, NewLink Genetics, Genmab, MedImmune, AstraZeneca, Syndax, Sun 
      Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore and 4SC, and received 
      research funding from Array, Bristol-Myers Squibb, Roche-Genentech and MSD. MDV 
      has served as a consultant to Bristol-Myers Squibb, Merck, Novartis, Pierre Fabre 
      and Sanofi. CR has served as a consultant to, or served on the board of 
      directors/advisors of Bristol-Myers Squibb, Pierre Fabre, Novartis, Amgen, Merck, 
      Roche, MSD and Sanofi. AA has received honoraria from Bristol-Myers Squibb, MSD, 
      Roche, Novartis, Pierre Fabre, Amgen, Sanofi and Merck. CLebbe has served on the 
      board of advisors/directors of Merck Serono, Novartis and Sanofi, and has served 
      as a consultant to, received research funding from or served on the board of 
      directors/advisors of Bristol-Myers Squibb, Roche and MSD. IMS has received 
      honoraria from MSD, Novartis, Bristol-Myers Squibb and Pierre Fabre. PR has 
      received honoraria from Bristol-Myers Squibb, Novartis, MSD, Roche, Pierre Fabre, 
      Amgen, Pfizer, Eli Lilly and Blueprint Medicines. CLoquai has served on the board 
      of advisors/directors of Bristol-Myers Squibb, MSD, Pierre Fabre, Roche, 
      Novartis, Sanofi, Biontech and Idera, and received honoraria from Bristol-Myers 
      Squibb, MSD, Pierre Fabre, Roche, Novartis, Sanofi and Kyowa Kirin. LM has served 
      on a medical board for Bristol-Myers Squibb, GlaxoSmithKline, Merck and Roche, 
      and has received travel fees from Bristol-Myers Squibb. OH has received research 
      funding from Amgen, Arcus, Astellas, AstraZeneca, BMS, Celldex, CytomX, 
      Genentech, GSK, Immunocore, Incyte, Iovance, Merck, Merck Serono, MedImmune, 
      NextCure, Novartis, Parker, Pfizer, Polynoma, Regeneron and Roche, served as a 
      consultant to Bristol-Myers Squibb, Amgen, Merck, Novartis and Roche, and 
      received honoraria from Bristol-Myers Squibb, Amgen, Array, Genentech, Novartis 
      and Sanofi. LB has served on the board of advisors/directors of Bristol-Myers 
      Squibb, Novartis, Merck, Roche, Incyte and Bayer, and received research funding 
      from Bristol-Myers Squibb. BD has received research funding from Bristol-Myers 
      Squibb, Roche and Novartis and honoraria from Bristol-Myers Squibb, Pierre Fabre 
      and Roche. DS has received honoraria from Bristol-Myers Squibb, Roche, Novartis, 
      Regeneron, Sanofi, Merck, Amgen, 4SC, Merck-EMD, Array, Pierre Fabre, Philiogen, 
      Incyte and Pfizer, and research funding from Bristol-Myers Squibb and Novartis. 
      CG has has served as a consultant to, or served on the board of 
      directors/advisors of Bristol-Myers Squibb, Amgen, MSD, NeraCare, Novartis, 
      Philogen, Roche and Sanofi, and research funding from Bristol-Myers Squibb, 
      NeraCare, Novartis, Roche and Sanofi. MN has received honoraria from Novartis, 
      Pierre Fabre and Bristol-Myers Squibb. J-JG has received honoraria from 
      Bristol-Myers Squibb, MSD, Roche, Novartis, Amgen, Pierre Fabre, Sun Pharma and 
      Sanofi. LT has received research funding from Bristol-Myers Squibb. GL has 
      received honoraria from and served as a consultant to Roche, MSD, Bristol-Myers 
      Squibb and Novartis. MS has received honoraria from BMS, Merck, Sanofi Genzyme 
      and Novartis. CH has received honoraria from, and served on the board of advisors 
      for Bristol-Myers Squibb, and honoraria from Amgen, MSD, Novartis, Pierre Fabre 
      and Roche. RG has received research funding and honoraria from Amgen, Novartis, 
      Pfizer and Johnson & Johnson, and honoraria from Bristol-Myers Squibb, Roche 
      Pharma, Merck Serono, Pierre Fabre, Sanofi, Merck, Almirall Hermal, LEO, 
      AstraZeneca, Sun Pharma and 4SC. FH and BS are employees of Bristol-Myers Squibb. 
      MM has received honoraria from Bristol-Myers Squibb, AstraZeneca, Roche, MSD, 
      Merck, GlaxoSmithKline and Incyte, and research funding from Bristol-Myers 
      Squibb.
EDAT- 2020/06/07 06:00
MHDA- 2021/05/22 06:00
PMCR- 2020/06/04
CRDT- 2020/06/07 06:00
PHST- 2020/03/11 00:00 [accepted]
PHST- 2020/06/07 06:00 [entrez]
PHST- 2020/06/07 06:00 [pubmed]
PHST- 2021/05/22 06:00 [medline]
PHST- 2020/06/04 00:00 [pmc-release]
AID - jitc-2019-000391 [pii]
AID - 10.1136/jitc-2019-000391 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2020 Jun;8(1):e000391. doi: 10.1136/jitc-2019-000391.