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Safety of Antibiotics in the Context of First-Line Chemo-Immunotherapy for Advanced NSCLC

Study findings point to potential to integrate prior antibiotic exposure in decision-making process for first-line treatment of advanced non-small cell lung cancer
18 Aug 2021
Cancer Immunology and Immunotherapy;  Lung and other thoracic tumours

In an international, multicentre study, Dr. Alessio Cortellini of the Imperial College London and Department of Surgery and Cancer, Hammersmith Hospital in London, UK and colleagues 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 chemo-immunotherapy 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 to first-line chemo-immunotherapy and should be integrated into currently available clinic-pathologic factors for guiding decisions for first-line treatment. Furthermore, there should be no concern in offering concurrent antibiotics during chemo-immunotherapy in that setting according the study findings. The study team published the results on 13 August 2021 in the Annals of Oncology.

The authors wrote in the background that composition and diversity of the gut microbiome has emerged as a tumour-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 chemo-immunotherapy 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 the investigators from 8 institutions to initiate an international, multicentre study to evaluate the impact of both prior and concurrent antibiotic exposure in a cohort of patients with advanced NSCLC treated with first-line chemo-immunotherapy combinations.

They retrospectively analyzed data from 302 patients with stage IV NSCLC treated in their institutions from December 2014 to October 2020, with data cut-off of January 2021. In total, 216 patients (71.5%) were former, and 61 patients (20.2%) were current smokers. In 274 evaluable patients (90.7%), PD-L1 tumour expression was ≥50% in 76 patients (25.2%), 1-49% 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 (OS) with hazard ratio (HR) 1.42 (95% confidence interval [CI] 0.91-2.22; p = 0.1207) and progression-free survival (PFS) with 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 overall response rate was found across groups with antibiotic exposure (42.6% vs. 57.4% p = 0.1794).

No differential effect was found depending on duration of prior antibiotic exposure (≥7 versus <7 days) and route of administration (intravenous versus oral).

Concurrent antibiotic exposure was not associated with OS with HR 1.29 (95% CI 0.91-1.84; p = 0.149) and PFS with HR 1.20 (95% CI 0.89-1.63; p = 0.222) when evaluated as time-varying covariate in multivariable analysis.

The authors wrote that prior antibiotic exposure does not impair clinical outcomes to first-line chemo-immunotherapy 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 chemo-immunotherapy combinations to avoid the detrimental effect of antibiotics.

The lack of effect on oncological outcomes suggests that in patients with chemotherapy-induced neutropenia and febrile neutropenia there should be no concern in offering concurrent antibiotic therapy during chemo-immunotherapy.

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.

Reference

Cortellini A, Ricciuti B, Facchinetti F, et al. Antibiotic-exposed patients with non-small cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy. Annals of Oncology; Published online 13 August 2021. DOI: https://doi.org/10.1016/j.annonc.2021.08.1744

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