Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy
Por:
Cortellini, A, Ricciuti, B, Facchinetti, F, Alessi, JVM, Venkatraman, D, Dall'Olio, FG, Cravero, P, Vaz, VR, Ottaviani, D, Majem, M, Piedra, A, Sullivan, I, Lee, KA, Lamberti, G, Hussain, N, Clark, J, Bolina, A, Barba, A, Benitez, JC, Gorria, T, Mezquita, L, Hoton, D, Nana, FA, Besse, B, Awad, MM, Pinato, DJ
Publicada:
1 nov 2021
Ahead of Print:
1 oct 2021
Resumen:
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 (a): 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.
Filiaciones:
Cortellini, A:
Univ LAquila, Dept Biotechnol & Appl Clin Sci, Laquila, Italy
Imperial Coll London, Hammersmith Hosp, Dept Surg & Canc, Div Canc, London, England
Ricciuti, B:
Harvard Med Sch, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Facchinetti, F:
Univ Paris Saclay, Inst Gustave Roussy, Biomarqueurs Predictifs & Nouvelles Strategies Th, INSERM, Villejuif, France
Alessi, JVM:
Harvard Med Sch, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Venkatraman, D:
Harvard Med Sch, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Dall'Olio, FG:
Gustave Roussy, Canc Med Dept, Villejuif, France
Cravero, P:
Harvard Med Sch, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Vaz, VR:
Harvard Med Sch, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Ottaviani, D:
Univ Coll London Hosp, Canc Div, London, England
Majem, M:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain
Piedra, A:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain
Sullivan, I:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain
Lee, KA:
Royal Marsden Hosp, Dept Med Oncol, London, England
Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomass Hosp, London, England
Lamberti, G:
Univ Bologna, S Orsola Malpighi Univ Hosp, Dept Expt Diagnost & Specialty Med, Alma Mater Studiorum, Bologna, Italy
Hussain, N:
Imperial Coll London, Hammersmith Hosp, Dept Surg & Canc, Div Canc, London, England
Clark, J:
Imperial Coll London, Hammersmith Hosp, Dept Surg & Canc, Div Canc, London, England
Bolina, A:
Imperial Coll London, Hammersmith Hosp, Dept Surg & Canc, Div Canc, London, England
Barba, A:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain
Benitez, JC:
Gustave Roussy, Canc Med Dept, Villejuif, France
Gorria, T:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Mezquita, L:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Hoton, D:
Clin Univ St Luc, Dept Pathol, Brussels, Belgium
Nana, FA:
Univ Catholique Louvain UCLouvain, Inst Rech Expt & Clin IREC, Pole Pneumol ORL & Dermatol PNEU, Brussels, Belgium
Besse, B:
Gustave Roussy, Canc Med Dept, Villejuif, France
Univ Paris Saclay, Sch Med, Villejuif, France
Awad, MM:
Harvard Med Sch, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Pinato, DJ:
Imperial Coll London, Hammersmith Hosp, Dept Surg & Canc, Div Canc, London, England
Univ Piemonte Orientale, Dept Translat Med, Div Oncol, Novara, Italy
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