Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy

A Cortellini; B Ricciuti; F Facchinetti; J V M Alessi; D Venkatraman; F G Dall'Olio; P Cravero; V R Vaz; D Ottaviani; M Majem; A Piedra; I Sullivan; K A Lee; G Lamberti; N Hussain; J Clark; A Bolina; A Barba; J C Benitez; T Gorría; L Mezquita; D Hoton; F Aboubakar Nana; B Besse; M M Awad; D J Pinato

doi:10.1016/j.annonc.2021.08.1744

Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy

Ann Oncol. 2021 Nov;32(11):1391-1399. doi: 10.1016/j.annonc.2021.08.1744. Epub 2021 Aug 13.

Authors

A Cortellini¹, B Ricciuti², F Facchinetti³, J V M Alessi², D Venkatraman², F G Dall'Olio⁴, P Cravero², V R Vaz², D Ottaviani⁵, M Majem⁶, A Piedra⁶, I Sullivan⁶, K A Lee⁷, G Lamberti⁸, N Hussain⁹, J Clark⁹, A Bolina⁹, A Barba⁶, J C Benitez⁴, T Gorría¹⁰, L Mezquita¹⁰, D Hoton¹¹, F Aboubakar Nana¹², B Besse¹³, M M Awad², D J Pinato¹⁴

Affiliations

¹ Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy; Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK. Electronic address: a.cortellini@imperial.ac.uk.
² Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
³ Université Paris-Saclay, Institut Gustave Roussy, Inserm, Biomarqueurs Prédictifs et Nouvelles Stratégies Thérapeutiques en Oncologie, Villejuif, France.
⁴ Cancer Medicine Department, Gustave Roussy, Villejuif, France.
⁵ Cancer Division, University College London Hospitals, London, UK.
⁶ Medical Oncology Department, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
⁷ Department of Medical Oncology, Royal Marsden Hospital, London, UK; Department of Twin Research and Genetic Epidemiology, St Thomas's Hospital, King's College London, London, UK.
⁸ Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
⁹ Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
¹⁰ Department of Medical Oncology, Hospital Clinic, Barcelona, Spain.
¹¹ Department of Pathology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
¹² Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Pneumologie, ORL et Dermatologie (PNEU), Université catholique de Louvain (UCLouvain), Brussels, Belgium.
¹³ Cancer Medicine Department, Gustave Roussy, Villejuif, France; University Paris-Saclay, School of Medicine, Villejuif, France.
¹⁴ Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.

PMID: 34400292
DOI: 10.1016/j.annonc.2021.08.1744

Abstract

Background: Prior antibiotic therapy (pATB) is known to impair efficacy of single-agent immune checkpoint inhibitors (ICIs), potentially through the induction of gut dysbiosis. Whether ATB also affects outcomes to chemo-immunotherapy combinations is still unknown.

Patients and methods: In this international multicentre study, we evaluated the association between pATB, concurrent ATB (cATB) and overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with non-small-cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy at eight referral institutions.

Results: Among 302 patients with stage IV NSCLC, 216 (71.5%) and 61 (20.2%) patients were former and current smokers, respectively. Programmed death-ligand 1 tumour expression in assessable patients (274, 90.7%) was ≥50% in 76 (25.2%), 1%-49% in 84 (27.9%) and <1% in 113 (37.5%). Multivariable analysis showed pATB-exposed patients to have similar OS {hazard ratio (HR) = 1.42 [95% confidence interval (CI): 0.91-2.22]; P = 0.1207} and PFS [HR = 1.12 (95% CI: 0.76-1.63); P = 0.5552], compared to unexposed patients, regardless of performance status. Similarly, no difference with respect to ORR was found across pATB exposure groups (42.6% versus 57.4%, P = 0.1794). No differential effect was found depending on pATB exposure duration (≥7 versus <7 days) and route of administration (intravenous versus oral). Similarly, cATB was not associated with OS [HR = 1.29 (95% CI: 0.91-1.84); P = 0.149] and PFS [HR = 1.20 (95% CI: 0.89-1.63); P = 0.222] when evaluated as time-varying covariate in multivariable analysis.

Conclusions: In contrast to what has been reported in patients receiving single-agent ICIs, pATB does not impair clinical outcomes to first-line chemo-immunotherapy of patients with NSCLC. pATB status should integrate currently available clinico-pathologic factors for guiding first-line treatment decisions, whilst there should be no concern in offering cATB during chemo-immunotherapy when needed.

Keywords: antibiotics; chemotherapy; immune checkpoint inhibitors; non-small-cell lung cancer; pembrolizumab; predictive factors.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents* / therapeutic use
Carcinoma, Non-Small-Cell Lung* / drug therapy
Humans
Immunotherapy
Lung Neoplasms* / drug therapy
Treatment Outcome

Substances

Anti-Bacterial Agents