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

• Published in: Annals of oncology Vol. 32; no. 11; pp. 1391 - 1399
• Main Authors: Cortellini, A., Ricciuti, B., Facchinetti, F., Alessi, J.V.M., Venkatraman, D., Dall'Olio, F.G., Cravero, P., Vaz, V.R., Ottaviani, D., Majem, M., Piedra, A., Sullivan, I., Lee, K.A., Lamberti, G., Hussain, N., Clark, J., Bolina, A., Barba, A., Benitez, J.C., Gorría, T., Mezquita, L., Hoton, D., Aboubakar Nana, F., Besse, B., Awad, M.M., Pinato, D.J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2021
• Subjects: Anti-Bacterial Agents - therapeutic use; antibiotics; Carcinoma, Non-Small-Cell Lung - drug therapy; chemotherapy; Humans; immune checkpoint inhibitors; Immunotherapy; Lung Neoplasms - drug therapy; non-small-cell lung cancer; pembrolizumab; predictive factors; Treatment Outcome; pembrolizumab; immune checkpoint inhibitors; antibiotics; chemotherapy; predictive factors; non-small-cell lung cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1016/j.annonc.2021.08.1744

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.
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.
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.
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.