Antibiotic use reduces efficacy of tyrosine kinase inhibitors in patients with advanced melanoma and non-small-cell lung cancer ☆

ESMO Open

article

N. Tinsley¹  C. Zhou³  S. Nahm¹  S. Rack¹  G.C.L. Tan⁵  P. Lorigan¹  F. Blackhall¹  N. Cook¹ 

[1] The Christie NHS Foundation Trust;Division of Cancer Sciences, University of Manchester;Cancer Research UK Manchester Institute, Cancer Biomarker Centre, University of Manchester;Sydney Medical School, The University of Sydney;Lewisham and Greenwich NHS Foundation Trust

关键词: tyrosine kinase inhibitors;    antibiotics;    melanoma;    lung cancer;   

DOI  :  10.1016/j.esmoop.2022.100430

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Antibiotic (ABX) use can reduce the efficacy of immune checkpoint inhibitors and chemotherapeutics. The effect for patients treated with targeted therapies, namely, small-molecule tyrosine kinase inhibitors (TKIs), is less known.Patients and methods Retrospective data were analysed for TKI-treated patients with advanced melanoma and non-small-cell lung cancer (NSCLC) between January 2015 and April 2017 at The Christie NHS Foundation Trust. Data on demographics, disease burden, lactate dehydrogenase (LDH) level, presence of brain metastases, ECOG performance status (PS) and ABX use were collected. Progression-free survival (PFS) and overall survival (OS) were compared between the ABX+ group (ABX within 2 weeks of TKI initiation-6 weeks after) and the ABX– group (no ABX during the same period).Results A total of 168 patients were included; 89 (53%) with NSCLC and 79 (47%) with melanoma. 55- (33%) patients received ABX. On univariable analysis, ABX+ patients demonstrated shorter PFS (208 versus 357 days; P = 0.008) and OS (294 versus 438 days; P = 0.024). Increased age, poorer PS and higher LDH were associated with shorter PFS and OS. On multivariable analysis, ABX use was independently associated with shorter PFS [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.05-2.34, P = 0.028] and OS (HR 2.19, 95% CI 1.44-3.32, P = 0.0002). The negative impact of ABX on OS was particularly pronounced for patients with PS of ≥2 (HR 3.82, 95% CI 1.18-12.36, P = 0.025).Conclusion For patients treated with TKIs, ABX use is independently associated with reduced PFS and OS and judicious use is warranted, particularly in patients with poorer PS.

【 授权许可】

CC BY|CC BY-NC-ND