In an international, multicenter study, researchers evaluated the impact of prior and concurrent antibiotic exposure in a cohort of patients with advanced non–small cell lung cancer (NSCLC) treated with first-line chemoimmunotherapy combinations. In contrast to what has been reported in patients receiving single-agent immunotherapy, they found that prior antibiotic exposure does not impair clinical outcomes of first-line chemoimmunotherapy and should be integrated into currently available clinicopathologic factors for guiding decisions about first-line treatment. These findings were published by Cortellini et al in Annals of Oncology.
The authors explained in their report that composition and diversity of the gut microbiome has emerged as a tumor-agnostic determinant of response to immune checkpoint inhibitors. It is known that prior antibiotic therapy impairs efficacy of immune checkpoint inhibitors administered as single agents, potentially through the induction of gut dysbiosis. However, whether antibiotics also affect outcomes to combinations of chemotherapy and immunotherapy is still unknown.
Patients with NSCLC benefit from synergistic efficacy of chemoimmunotherapy combinations, which have led to increase in survival in metastatic setting, but there was no evidence to suggest whether antibiotic-mediated dysbiosis can influence outcomes in these patients. It prompted investigators from eight institutions to initiate an international, multicenter study to evaluate the impact of both prior and concurrent antibiotic exposure in a cohort of patients with advanced NSCLC treated with first-line chemoimmunotherapy combinations.
Photo credit: Getty
Study Methods and Results
The researchers retrospectively analyzed data from 302 patients with stage IV NSCLC treated in their institutions from December 2014 to October 2020, with data cutoff of January 2021. In total, 216 patients (71.5%) were former smokers and 61 patients (20.2%) were current smokers. In 274 evaluable patients (90.7%), PD-L1 tumor expression was ≥ 50% in 76 patients (25.2%), 1% to 49% in 84 patients (27.9%), and < 1% in 113 patients (37.5%).
Multivariable analysis showed that patients with prior antibiotic exposure had similar overall survival (hazard ratio [HR] = 1.42, 95% confidence interval [CI] = 0.91–2.22, P = .1207) and progression-free survival (HR = 1.12, 95% CI = 0.76–1.63, P = .5552), compared to unexposed patients, regardless of performance status. Similarly, no difference in overall response rate was found across groups with antibiotic exposure (42.6% vs 57.4%, P = .1794).
No differential effect was found depending on duration of prior antibiotic exposure (≥ 7 vs < 7 days) and route of administration (intravenous vs oral). Concurrent antibiotic exposure was not associated with overall survival (HR = 1.29, 95% CI = 0.91–1.84, P = .149) and progression-free survival (HR = 1.20, 95% CI = 0.89–1.63, P = .222) when evaluated as time-varying covariates in multivariable analysis.
The authors wrote that prior antibiotic exposure does not impair clinical outcomes to first-line chemoimmunotherapy combination treatment among patients with advanced NSCLC. They commented that patients with PD-L1–positive NSCLC and prior antibiotic exposure might be best served by chemoimmunotherapy combinations to avoid the detrimental effect of antibiotics.
The lack of effect on oncologic outcomes suggests that in patients with chemotherapy-induced neutropenia and febrile neutropenia, there should be no concern about offering concurrent antibiotic therapy during chemoimmunotherapy. The authors concluded that further mechanistic investigation is needed in prospective studies to elucidate stratification potential for prior antibiotic status and the interplay between gut microbiome diversity, systemic antibiotics, and chemotherapy-enhanced anticancer immunity.
Disclosure: For full disclosures of the study authors, visit annalsofoncology.org.
