PMID- 33154150
OWN - NLM
STAT- MEDLINE
DCOM- 20210916
LR  - 20210916
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 8
IP  - 2
DP  - 2020 Nov
TI  - Integrated analysis of concomitant medications and oncological outcomes from 
      PD-1/PD-L1 checkpoint inhibitors in clinical practice.
LID - 10.1136/jitc-2020-001361 [doi]
LID - e001361
AB  - BACKGROUND: Concomitant medications, such as steroids, proton pump inhibitors 
      (PPI) and antibiotics, might affect clinical outcomes with immune checkpoint 
      inhibitors. METHODS: We conducted a multicenter observational retrospective study 
      aimed at evaluating the impact of concomitant medications on clinical outcomes, 
      by weighing their associations with baseline clinical characteristics (including 
      performance status, burden of disease and body mass index) and the underlying 
      causes for their prescription. This analysis included consecutive stage IV 
      patients with cancer, who underwent treatment with single agent antiprogrammed 
      death-1/programmed death ligand-1 (PD-1/PD-L1) with standard doses and schedules 
      at the medical oncology departments of 20 Italian institutions. Each medication 
      taken at the immunotherapy initiation was screened and collected into key 
      categories as follows: corticosteroids, antibiotics, gastric acid suppressants 
      (including proton pump inhibitors - PPIs), statins and other lipid-lowering 
      agents, aspirin, anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), 
      ACE inhibitors/Angiotensin II receptor blockers, calcium antagonists, beta-blockers, 
      metformin and other oral antidiabetics, opioids. RESULTS: From June 2014 to March 
      2020, 1012 patients were included in the analysis. Primary tumors were: non-small 
      cell lung cancer (52.2%), melanoma (26%), renal cell carcinoma (18.3%) and others 
      (3.6%). Baseline statins (HR 1.60 (95% CI 1.14 to 2.25), p=0.0064), aspirin (HR 
      1.47 (95% CI 1.04 to 2.08, p=0.0267) and beta-blockers (HR 1.76 (95% CI 1.16 to 
      2.69), p=0.0080) were confirmed to be independently related to an increased 
      objective response rate. Patients receiving cancer-related steroids (HR 1.72 (95% 
      CI 1.43 to 2.07), p<0.0001), prophylactic systemic antibiotics (HR 1.85 (95% CI 
      1.23 to 2.78), p=0.0030), prophylactic gastric acid suppressants (HR 1.29 (95% CI 
      1.09 to 1.53), p=0.0021), PPIs (HR 1.26 (95% CI 1.07 to 1.48), p=0.0050), 
      anticoagulants (HR 1.43 (95% CI: 1.16 to 1.77), p=0.0007) and opioids (HR 1.71 
      (95% CI 1.28 to 2.28), p=0.0002) were confirmed to have a significantly higher 
      risk of disease progression. Patients receiving cancer-related steroids (HR 2.16 
      (95% CI 1.76 to 2.65), p<0.0001), prophylactic systemic antibiotics (HR 1.93 (95% 
      CI 1.25 to 2.98), p=0.0030), prophylactic gastric acid suppressants (HR 1.29 (95% 
      CI 1.06 to 1.57), p=0.0091), PPI (HR 1.26 (95% CI 1.04 to 1.52), p=0.0172), 
      anticoagulants (HR 1.45 (95% CI 1.14 to 1.84), p=0.0024) and opioids (HR 1.53 
      (95% CI 1.11 to 2.11), p=0.0098) were confirmed to have a significantly higher 
      risk of death. CONCLUSION: We confirmed the association between baseline steroids 
      administered for cancer-related indication, systemic antibiotics, PPIs and worse 
      clinical outcomes with PD-1/PD-L1 checkpoint inhibitors, which can be assumed to 
      have immune-modulating detrimental effects.
CI  - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Cortellini, Alessio
AU  - Cortellini A
AUID- ORCID: 0000-0002-1209-5735
AD  - Department of Biotechnology and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila, Italy alessiocortellini@gmail.com.
AD  - Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy.
FAU - Tucci, Marco
AU  - Tucci M
AD  - Medical Oncology Unit, Department of Biomedical Sciences and Human Oncology, 
      University of Bari, Bary, Italy.
AD  - National Cancer Research Center, Tumori Institute IRCCS Giovanni Paolo II, Bari, 
      Italy.
FAU - Adamo, Vincenzo
AU  - Adamo V
AD  - Medical Oncology, Department of Human Pathology, A.O. Papardo, University of 
      Messina, Messina, Italy.
FAU - Stucci, Luigia Stefania
AU  - Stucci LS
AD  - Medical Oncology Unit, Department of Biomedical Sciences and Human Oncology, 
      University of Bari, Bary, Italy.
FAU - Russo, Alessandro
AU  - Russo A
AD  - Medical Oncology, Department of Human Pathology, A.O. Papardo, University of 
      Messina, Messina, Italy.
FAU - Tanda, Enrica Teresa
AU  - Tanda ET
AD  - IRCCS Ospedale Policlinico San Martino, Genova, Italy.
FAU - Spagnolo, Francesco
AU  - Spagnolo F
AD  - IRCCS Ospedale Policlinico San Martino, Genova, Italy.
FAU - Rastelli, Francesca
AU  - Rastelli F
AD  - Medical Oncology, ASUR District Area 4 Fermo, Fermo, Italy.
FAU - Bisonni, Renato
AU  - Bisonni R
AD  - Medical Oncology, ASUR District Area 4 Fermo, Fermo, Italy.
FAU - Santini, Daniele
AU  - Santini D
AD  - Medical Oncology, Campus Bio-Medico University, Rome, Italy.
FAU - Russano, Marco
AU  - Russano M
AD  - Medical Oncology, Campus Bio-Medico University, Rome, Italy.
FAU - Anesi, Cecilia
AU  - Anesi C
AD  - Medical Oncology, Campus Bio-Medico University, Rome, Italy.
FAU - Giusti, Raffaele
AU  - Giusti R
AD  - Medical Oncology Unit, Sant'Andrea Hospital of Rome, Rome, Italy.
FAU - Filetti, Marco
AU  - Filetti M
AD  - Medical Oncology Unit, Sant'Andrea Hospital of Rome, Rome, Italy.
FAU - Marchetti, Paolo
AU  - Marchetti P
AD  - Medical Oncology Unit, Sant'Andrea Hospital of Rome, Rome, Italy.
AD  - Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, 
      Italy.
AD  - Medical Oncology Unit B, Policlinico Umberto I, Sapienza University of Rome, 
      Roma, Italy.
FAU - Botticelli, Andrea
AU  - Botticelli A
AD  - Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, 
      Italy.
FAU - Gelibter, Alain
AU  - Gelibter A
AD  - Medical Oncology Unit B, Policlinico Umberto I, Sapienza University of Rome, 
      Roma, Italy.
FAU - Occhipinti, Mario Alberto
AU  - Occhipinti MA
AD  - Medical Oncology Unit B, Policlinico Umberto I, Sapienza University of Rome, 
      Roma, Italy.
FAU - Marconcini, Riccardo
AU  - Marconcini R
AD  - Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
FAU - Vitale, Maria Giuseppa
AU  - Vitale MG
AD  - Medical Oncology, University Hospital Modena, Modena, Italy.
FAU - Nicolardi, Linda
AU  - Nicolardi L
AD  - UOC Oncologia Padova Sud, Azienda ULSS 6 Euganea, Padova, Italy.
FAU - Chiari, Rita
AU  - Chiari R
AD  - UOC Oncologia Padova Sud, Azienda ULSS 6 Euganea, Padova, Italy.
FAU - Bareggi, Claudia
AU  - Bareggi C
AD  - Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore di Milano 
      Policlinico, Milano, Italy.
FAU - Nigro, Olga
AU  - Nigro O
AD  - Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, 
      Varese, Italy.
FAU - Tuzi, Alessandro
AU  - Tuzi A
AD  - Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, 
      Varese, Italy.
FAU - De Tursi, Michele
AU  - De Tursi M
AD  - Department of Medical, Oral and Biotechnological Sciences, Gabriele d'Annunzio 
      University of Chieti and Pescara, Chieti, Italy.
FAU - Petragnani, Nicola
AU  - Petragnani N
AD  - Department of Psychological, Health and Territorial Sciences, University G. 
      D'Annunzio of Chieti and Pescara, Chieti, Italy.
FAU - Pala, Laura
AU  - Pala L
AD  - Division of Medical Oncology for Melanoma, Sarcoma and Rare Tumors, IEO European 
      Institute of Oncology IRCCS, Milan, Italy.
FAU - Bracarda, Sergio
AU  - Bracarda S
AD  - Medical Oncology, Azienda Ospedaliera S. Maria, Terni, Italy.
FAU - Macrini, Serena
AU  - Macrini S
AD  - Medical Oncology, Azienda Ospedaliera S. Maria, Terni, Italy.
FAU - Inno, Alessandro
AU  - Inno A
AD  - Oncology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Italy.
FAU - Zoratto, Federica
AU  - Zoratto F
AD  - Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy.
FAU - Veltri, Enzo
AU  - Veltri E
AD  - Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy.
FAU - Di Cocco, Barbara
AU  - Di Cocco B
AD  - Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy.
FAU - Mallardo, Domenico
AU  - Mallardo D
AD  - Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto 
      Nazionale Tumori IRCCS Fondazione "G. Pascale", Napoli, Italy.
FAU - Vitale, Maria Grazia
AU  - Vitale MG
AD  - Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto 
      Nazionale Tumori IRCCS Fondazione "G. Pascale", Napoli, Italy.
FAU - Pinato, David James
AU  - Pinato DJ
AUID- ORCID: 0000-0002-3529-0103
AD  - Division of Cancer, Department of Surgery and Cancer, Imperial College London, 
      Hammersmith Hospital, London, UK.
FAU - Porzio, Giampiero
AU  - Porzio G
AD  - Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy.
FAU - Ficorella, Corrado
AU  - Ficorella C
AD  - Department of Biotechnology and Applied Clinical Sciences, University of 
      L'Aquila, L'Aquila, Italy.
AD  - Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy.
FAU - Ascierto, Paolo Antonio
AU  - Ascierto PA
AUID- ORCID: 0000-0002-8322-475X
AD  - Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto 
      Nazionale Tumori IRCCS Fondazione "G. Pascale", Napoli, Italy.
LA  - eng
GR  - PS3416/WT_/Wellcome Trust/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
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)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Humans
MH  - Immune Checkpoint Inhibitors/pharmacology/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Young Adult
PMC - PMC7646355
OTO - NOTNLM
OT  - immunotherapy
COIS- Competing interests: AC received speaker fees and grant consultancies from Roche, 
      MSD, BMS, AstraZeneca, Novartis, Astellas. RG received speaker fees and grant 
      consultancies from AstraZeneca and Roche. MGV received speaker fees, grant 
      consultancies and travel support from BMS, Ipsen, Novartis, Pfizer, Astellas, 
      Jansen and Pierre-Fabre. AR received grant consultancies from AstraZeneca and 
      MSD. RM received grant consultancies from Pierre-Fabre, MSD, Incyte, BMS, and 
      Roche. FS received speaker fees and grant consultancies from Roche, Novartis, 
      BMS, MSD, Pierre-Fabre, Sanofi, Merck and Sunpharma. DP received lecture fees 
      from ViiV Healthcare, Bayer Healthcare and travel expenses from BMS and Bayer 
      Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, Astra Zeneca; 
      received research funding (to institution) from MSD, BMS. PAA received speaker 
      fees and grant consultancies from BMS, Roche-Genentech, MSD, Dohme, Array, 
      Novartis, Merck-Serono, Pierre-Fabre, Incyte, New Link Genetics, Genmab, 
      Medimmune, AstraZeneca, Syndax, SunPharma, Sanofi, Idera, Ultimovacs, Sandoz, 
      Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim; he also 
      received research funds from BMS, Roche-Genentech, Array.
EDAT- 2020/11/07 06:00
MHDA- 2021/09/18 06:00
PMCR- 2020/11/05
CRDT- 2020/11/06 05:51
PHST- 2020/08/28 00:00 [accepted]
PHST- 2020/11/06 05:51 [entrez]
PHST- 2020/11/07 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2020/11/05 00:00 [pmc-release]
AID - jitc-2020-001361 [pii]
AID - 10.1136/jitc-2020-001361 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2020 Nov;8(2):e001361. doi: 10.1136/jitc-2020-001361.