PMID- 32115349
OWN - NLM
STAT- MEDLINE
DCOM- 20210106
LR  - 20210106
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 31
IP  - 4
DP  - 2020 Apr
TI  - Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung 
      cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses 
      of the OAK and POPLAR trials.
PG  - 525-531
LID - S0923-7534(20)35927-5 [pii]
LID - 10.1016/j.annonc.2020.01.006 [doi]
AB  - BACKGROUND: Preclinical data have shown that proton pump inhibitors (PPI) can 
      modulate the microbiome, and single-arm studies suggested that antibiotics (ATB) 
      may decrease the efficacy of immune checkpoint inhibitors (ICI), but randomized 
      controlled trial data are lacking. This pooled analysis evaluated the effect of 
      ATB and PPI on outcome in patients randomized between ICI and chemotherapy. 
      PATIENTS AND METHODS: This retrospective analysis used pooled data from the phase 
      II POPLAR (NCT01903993) and phase III OAK (NCT02008227) trials, which included 
      1512 patients with previously treated non-small-cell lung cancer (NSCLC) randomly 
      assigned to receive atezolizumab (n = 757) or docetaxel (n = 755). The main 
      objective of this analysis was to assess the impact of ATB and PPI use on overall 
      survival (OS) and progression-free survival (PFS). RESULTS: A total of 169 
      (22.3%) patients in the atezolizumab group and 202 (26.8%) in the docetaxel group 
      received ATB, and 234 (30.9%) and 260 (34.4%), respectively, received PPI. 
      Multivariate analysis in all patients revealed that ATB were associated with 
      shorter OS [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], as 
      was PPI (HR 1.26, 95% CI 1.10-1.44). Within the atezolizumab population, OS was 
      significantly shorter in patients who received ATB (8.5 versus 14.1 months, HR 
      1.32, 95% CI 1.06-1.63, P = 0.01) or PPI (9.6 versus 14.5 months, HR 1.45, 95% CI 
      1.20-1.75, P = 0.0001). PPI use was associated with shorter PFS in the 
      atezolizumab population (1.9 versus 2.8 months, HR 1.30, 95% CI 1.10-1.53, P = 
      0.001). There was no association between ATB and PPI use and PFS or OS within the 
      docetaxel population. CONCLUSION: In this unplanned analysis from two randomized 
      trials, data suggest that ATB or PPI use in patients with metastatic NSCLC is 
      associated with poor outcome and may influence the efficacy of ICI.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Chalabi, M
AU  - Chalabi M
AD  - Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The 
      Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, 
      Amsterdam, The Netherlands. Electronic address: m.chalabi@nki.nl.
FAU - Cardona, A
AU  - Cardona A
AD  - PD Biometrics, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Nagarkar, D R
AU  - Nagarkar DR
AD  - Cancer Immunology, Genentech, Inc., South San Francisco, USA.
FAU - Dhawahir Scala, A
AU  - Dhawahir Scala A
AD  - PD Biometrics, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Gandara, D R
AU  - Gandara DR
AD  - Department of Thoracic Oncology, UC Davis Comprehensive Cancer Center, 
      Sacramento, USA.
FAU - Rittmeyer, A
AU  - Rittmeyer A
AD  - Department of Thoracic Oncology, Pulmonary Clinic Immenhausen, Immenhausen, 
      Germany.
FAU - Albert, M L
AU  - Albert ML
AD  - Cancer Immunology, Genentech, Inc., South San Francisco, USA.
FAU - Powles, T
AU  - Powles T
AD  - Centre for Experimental Cancer Medicine, Barts Cancer Institute, London, UK.
FAU - Kok, M
AU  - Kok M
AD  - Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The 
      Netherlands; Tumor Biology and Immunology, Netherlands Cancer Institute, 
      Amsterdam, The Netherlands.
FAU - Herrera, F G
AU  - Herrera FG
AD  - Immune Oncology Service, Lausanne University Hospital, Ludwig Institute for 
      Cancer Research, Lausanne, Switzerland. Electronic address: 
      Fernanda.Herrera@chuv.ch.
CN  - imCORE working group of early career investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT01903993
SI  - ClinicalTrials.gov/NCT02008227
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200116
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Proton Pump Inhibitors)
RN  - 52CMI0WC3Y (atezolizumab)
SB  - IM
CIN - Ann Oncol. 2020 Dec;31(12):1779-1780. PMID: 32976935
MH  - Anti-Bacterial Agents
MH  - Antibodies, Monoclonal, Humanized
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - Humans
MH  - *Lung Neoplasms/drug therapy
MH  - Proton Pump Inhibitors
MH  - Retrospective Studies
OTO - NOTNLM
OT  - antibiotics
OT  - immune checkpoint inhibitors
OT  - lung cancer
OT  - microbiota
OT  - proton pump inhibitors
COIS- Disclosure MC reports grants to the institute from Bristol Myers Squibb/II-ON and 
      Roche, outside the submitted work. AC and ADS are employees of F. Hoffmann-La 
      Roche Ltd. DRN is an employee of Genentech Inc. and reports ownership of stocks 
      from F. Hoffmann-La Roche Ltd. DRG reports a consulting or advisory role for 
      AstraZeneca, Celgene, CellMax Life, Genentech, Guardant Health, Lilly, Liquid 
      Genomics, Inc., and research funding from AstraZeneca/MedImmune (Inst) and 
      Genentech (Inst). AR reports a consultant or advisory role for AbbVie, 
      AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, MSD, 
      Pfizer, and Roche/Genentech. MLA is an employee of Genentech Inc. and is now an 
      employee of Insitro. TP reports honoraria received from Novartis, BMS, Merck, 
      Pfizer, Roche, and AstraZeneca. MK reports funding and a speaker's fee to the 
      institute from BMS, Roche and an unpaid advisory role for BMS, outside 
      the submitted work. FGH reports research funding from BMS, Accuray Inc., 
      Bioprotect, and Prostate Cancer Foundation.
EDAT- 2020/03/03 06:00
MHDA- 2021/01/07 06:00
CRDT- 2020/03/03 06:00
PHST- 2019/07/30 00:00 [received]
PHST- 2019/12/08 00:00 [revised]
PHST- 2020/01/04 00:00 [accepted]
PHST- 2020/03/03 06:00 [pubmed]
PHST- 2021/01/07 06:00 [medline]
PHST- 2020/03/03 06:00 [entrez]
AID - S0923-7534(20)35927-5 [pii]
AID - 10.1016/j.annonc.2020.01.006 [doi]
PST - ppublish
SO  - Ann Oncol. 2020 Apr;31(4):525-531. doi: 10.1016/j.annonc.2020.01.006. Epub 2020 
      Jan 16.