PMID- 36368251
OWN - NLM
STAT- MEDLINE
DCOM- 20221201
LR  - 20230105
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 177
DP  - 2022 Dec
TI  - Comparative assessment of early mortality risk upon immune checkpoint inhibitors 
      alone or in combination with other agents across solid malignancies: a systematic 
      review and meta-analysis.
PG  - 175-185
LID - S0959-8049(22)00771-7 [pii]
LID - 10.1016/j.ejca.2022.09.031 [doi]
AB  - BACKGROUND: The early crossing of survival curves in randomised clinical trials 
      (RCTs) with immune checkpoint blockers suggests an excess of mortality in the 
      first months of treatment. However, the exact estimation of the early death (ED) 
      rate, the comparison between ED upon immune checkpoint inhibitors (ICI) alone or 
      in combination with other agents and the impact of tumour type, and PD-L1 
      expression on ED are unknown. METHODS: RCTs comparing ICI alone (ICI-only group) 
      or in combination with other non-ICI therapies (ICI-OT group) (experimental arms) 
      versus non-ICI treatments (control arm) were included. ED was defined as death 
      within the first 3 months of treatment. The primary outcome was the comparison of 
      ED between experimental and control arms, and the secondary outcome was the 
      comparison of ED risk between ICI-only and ICI-OT. ED rates estimated by risk 
      ratio (RR) were pooled by random effect model. RESULTS: A total of 56 RCTs 
      (40,215 participants, 14 cancer types) were included. ED occurred in 14.2% and 
      6.7% of patients in ICI-only and ICI-OT groups, respectively. ED risk 
      significantly increased with ICI-only (RR: 1.29, 95% CI 1.05-1.57) versus non-ICI 
      therapies, while it was lower with ICI-OT versus non-ICI treatments (RR: 0.81, 
      95% CI 0.73-0.90). ED risk was significantly higher upon ICI-only compared to 
      ICI-OT (RR: 1.57, 95% CI 1.26-1.95). Gastric and urothelial carcinoma were at 
      higher risk of ED. PD-L1 expression and ICI drug classes were not associated with 
      ED. CONCLUSIONS: ED upon first-line ICI is a clinically relevant phenomenon 
      across solid malignancies, not predictable by PD-L1 expression but preventable 
      through the addition of other treatments to ICI.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Viscardi, Giuseppe
AU  - Viscardi G
AD  - Medical Oncology, Department of Precision Medicine, Universita Degli Studi Della 
      Campania "Luigi Vanvitelli", Naples, Italy; Department of Pneumology and 
      Oncology, AORN Ospedali Dei Colli, Naples, Italy. Electronic address: 
      https://twitter.com/@giusvisc.
FAU - Tralongo, Antonino C
AU  - Tralongo AC
AD  - Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 
      Milan, Italy; Medical Oncology Unit, Umberto I Hospital, Azienda Sanitaria 
      Provinciale (ASP) Siracusa, Siracusa, Italy.
FAU - Massari, Francesco
AU  - Massari F
AD  - Department of Experimental, Diagnostic and Specialty Medicine, University of 
      Bologna, Bologna, Italy; Medical Oncology, IRCCS Azienda 
      Ospedaliero-Universitaria di Bologna, Bologna, Italy.
FAU - Lambertini, Matteo
AU  - Lambertini M
AD  - Department of Internal Medicine and Medical Specialties (DiMI), School of 
      Medicine, University of Genova, Genova, Italy; Department of Medical Oncology, UO 
      Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, 
      Italy.
FAU - Mollica, Veronica
AU  - Mollica V
AD  - Department of Experimental, Diagnostic and Specialty Medicine, University of 
      Bologna, Bologna, Italy; Medical Oncology, IRCCS Azienda 
      Ospedaliero-Universitaria di Bologna, Bologna, Italy.
FAU - Rizzo, Alessandro
AU  - Rizzo A
AD  - SSD Oncologia Medica per La Presa in Carico Globale Del Paziente Oncologico "Don 
      Tonino Bello", IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
FAU - Comito, Francesca
AU  - Comito F
AD  - Department of Experimental, Diagnostic and Specialty Medicine, University of 
      Bologna, Bologna, Italy; Medical Oncology, IRCCS Azienda 
      Ospedaliero-Universitaria di Bologna, Bologna, Italy.
FAU - Di Liello, Raimondo
AU  - Di Liello R
AD  - Clinical Trials Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, 
      Naples, Italy.
FAU - Alfieri, Salvatore
AU  - Alfieri S
AD  - Head and Neck Medical Oncology 3 Department, Fondazione IRCCS Istituto Nazionale 
      Dei Tumori, Milan, Italy.
FAU - Imbimbo, Martina
AU  - Imbimbo M
AD  - Department of Oncology, Immuno-oncology Service, Lausanne University Hospital 
      (CHUV), Lausanne, Switzerland.
FAU - Della Corte, Carminia M
AU  - Della Corte CM
AD  - Medical Oncology, Department of Precision Medicine, Universita Degli Studi Della 
      Campania "Luigi Vanvitelli", Naples, Italy.
FAU - Morgillo, Floriana
AU  - Morgillo F
AD  - Medical Oncology, Department of Precision Medicine, Universita Degli Studi Della 
      Campania "Luigi Vanvitelli", Naples, Italy.
FAU - Simeon, Vittorio
AU  - Simeon V
AD  - Medical Statistics Unit, Department of Mental Health and Public Medicine, 
      Universita Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy.
FAU - Lo Russo, Giuseppe
AU  - Lo Russo G
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, 
      Milan, Italy.
FAU - Proto, Claudia
AU  - Proto C
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, 
      Milan, Italy.
FAU - Prelaj, Arsela
AU  - Prelaj A
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, 
      Milan, Italy.
FAU - De Toma, Alessandro
AU  - De Toma A
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, 
      Milan, Italy.
FAU - Galli, Giulia
AU  - Galli G
AD  - Medical Oncology Unit, Policlinico San Matteo Fondazione IRCCS, Pavia, Italy.
FAU - Signorelli, Diego
AU  - Signorelli D
AD  - Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
FAU - Ciardiello, Fortunato
AU  - Ciardiello F
AD  - Medical Oncology, Department of Precision Medicine, Universita Degli Studi Della 
      Campania "Luigi Vanvitelli", Naples, Italy.
FAU - Remon, Jordi
AU  - Remon J
AD  - Department of Medical Oncology, Centro Integral Oncologico Clara Campal 
      (HM-CIOCC), Hospital Delfos, Barcelona, Spain.
FAU - Chaput, Nathalie
AU  - Chaput N
AD  - Laboratory of Immunomonitoring in Oncology, Gustave Roussy, Villejuif, France; 
      Faculty of Pharmacy, University Paris-Saclay, Chatenay-Malabry, France.
FAU - Besse, Benjamin
AU  - Besse B
AD  - Cancer Medicine Department, Gustave Roussy, Villejuif, France; Faculty of 
      Medicine, University Paris-Saclay, Le Kremlin Bicetre, France.
FAU - de Braud, Filippo
AU  - de Braud F
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, 
      Milan, Italy.
FAU - Garassino, Marina C
AU  - Garassino MC
AD  - Department of Medicine, University of Chicago; University of Chicago 
      Comprehensive Cancer Center, Chicago, USA.
FAU - Torri, Valter
AU  - Torri V
AD  - Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 
      Milan, Italy.
FAU - Cinquini, Michela
AU  - Cinquini M
AD  - Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 
      Milan, Italy.
FAU - Ferrara, Roberto
AU  - Ferrara R
AD  - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, 
      Milan, Italy. Electronic address: roberto.ferrara@istitutotumori.mi.it.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
DEP - 20221005
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Humans
MH  - B7-H1 Antigen
MH  - *Immune Checkpoint Inhibitors/therapeutic use
MH  - *Neoplasms/drug therapy/mortality
OTO - NOTNLM
OT  - Breast cancer
OT  - Chemotherapy
OT  - Early mortality
OT  - Gastrointestinal cancer
OT  - Genitourinary cancer
OT  - Immune checkpoint blockers
OT  - Immunotherapy
OT  - Lung cancer
OT  - Melanoma
OT  - Meta-analysis
COIS- Conflict of interest statement The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Prof Matteo Lambertini: advisory role for Roche, Lilly, Novartis, 
      Pfizer, Astrazeneca, MSD, Seagen, Gilead and speaker honoraria from Roche, Lilly, 
      Novartis, Pfizer, Sandoz, Ipsen, Libbs, Knight. Dr Raimondo Di Liello: consultant 
      Janssen, educational Astellas. Dr Martina Imbimbo: independent safety board 
      member for Immatics. Dr Carminia Maria Della Corte: advisory board for MSD and 
      Astrazeneca. Prof Floriana Morgillo: BMS, MSD, Astrazeneca, Incyte 
      (Consultory/Advisory relationship). Dr Giuseppe Lo Russo: personal fees from 
      AstraZeneca, Italfarmaco, Lilly, Novartis, Pfizer, and Roche; support for 
      attending meetings/travel from Bristol-Myers Squibb, Italfarmaco, Merck Sharp & 
      Dohme, and Roche; and participation as a DSMB or advisory board member for 
      AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Sanofi. Dr Claudia 
      Proto: personal fees from BMS and MSD. Dr Arsela Prelaj: personal fees from 
      Roche, AstraZeneca and BMS. Dr Diego Signorelli: personal fees from Astrazeneca, 
      BMS, MSD, Sanofi, Boehringer Ingelheim, Roche. Prof Fortunato Ciardiello: Merck, 
      Roche, Amgen, Bayer, Servier, Symphogen, Pfizer (Consultant/Avisory 
      relationship), Roche, Merck, Amgen, Bayer, Ipsen (Research funding). Dr Nathalie 
      Chaput: sponsored research from AstraZeneca, GSK, Roche, Sanofi, Cytune Pharma, 
      Gilead, Servier. Lectures and educational activities: Gilead and Servier. Dr 
      Jordi Remon: advisory board: MSD, Boehringer Ingelheim, BMS, Astrazeneca, Roche; 
      Bayer, Janssen. Speaker: Pfizer, Janssen; travel reimbursement: Ose 
      immunotherapeutics, BMS, Astrazeneca, Roche. Prof Benjamin Besse: grants from 
      AstraZeneca, Pfizer, Eli Lilly, Onxeo, Bristol Myers Squibb, Inivata, AbbVie, 
      Amgen, Blueprint Medicines, Celgene, GlaxoSmithKline, Ignyta, Ipsen, Merck KGaA, 
      MSD Oncology, Nektar, PharmaMar, Sanofi, Spectrum Pharmaceuticals, Takeda, 
      Tiziana Therapeutics, Cristal Therapeutics, Daiichi Sankyo, Janssen Oncology, OSE 
      Immunotherapeutics, BeiGene, Boehringer Ingelheim, Genentech, Servier, Tolero 
      Pharmaceuticals. Prof Filippo De Braud: Consultant Advisory Board: Roche, EMD 
      Serono, NMS Nerviano Medical Science, Sanofi, MSD, Novartis, Incyte, BMS, 
      Menarini. Speaker: BMS, Healthcare Research & Pharmacoepidemiology, Merck Group, 
      ACCMED, Nadirex, MSD, Pfizer, Servier, Sanofi, Roche, AMGEN, Incyte, Dephaforum. 
      Principal Investigator for Novartis, F. Hoffmann-LaRoche Ltd, BMS, Ignyta 
      Operating INC, Merck Sharp & Dohme Spa, Kymab, Pfizer, Tesaro, MSD, MedImmune 
      LCC, Exelixis Inc., LOXO Oncology Incorporated, DAICHI SANKIO Dev. Limited, 
      Basilea Pharmaceutica International AG, Janssen-Cilag International NV, Merck 
      KGAA. Prof Marina Chiara Garassino: personal financial interests with the 
      following organisations: AstraZeneca, MSD International GmbH, BMS, Boehringer 
      Ingelheim Italia S. p.A, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, 
      Novartis, Pfizer, Roche, Takeda; institutional financial interests with the 
      following organisations: Eli Lilly, MSD, Pfizer (MISP), AstraZeneca, MSD 
      International GmbH, BMS, Boehringer Ingelheim Italia S. p.A, Celgene, Ignyta, 
      Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda, Tiziana, Foundation 
      Medicine; funding from the following organisations: AIRC, AIFA, Italian Moh, 
      TRANSCAN. All the other authors have no conflicts to declare. Dr Roberto Ferrara: 
      advisory board for Beigene and MSD. All the other authors (Dr Giuseppe Viscardi, 
      Dr Antonino Carmelo Tralongo, Dr Francesco Massari, Dr Veronica Mollica, Dr 
      Alessandro Rizzo, Dr Francesca Comito, Dr Salvatore Alfieri, Dr Vittorio Simeon, 
      Dr Alessandro De Toma, Dr Giulia Galli, Dr Valter Torri, Dr Michela Cinquini) 
      have no conflicts to declare.
EDAT- 2022/11/12 06:00
MHDA- 2022/12/01 06:00
CRDT- 2022/11/11 18:31
PHST- 2022/08/18 00:00 [received]
PHST- 2022/09/24 00:00 [accepted]
PHST- 2022/11/12 06:00 [pubmed]
PHST- 2022/12/01 06:00 [medline]
PHST- 2022/11/11 18:31 [entrez]
AID - S0959-8049(22)00771-7 [pii]
AID - 10.1016/j.ejca.2022.09.031 [doi]
PST - ppublish
SO  - Eur J Cancer. 2022 Dec;177:175-185. doi: 10.1016/j.ejca.2022.09.031. Epub 2022 
      Oct 5.