Antibiotic use and efficacy of small molecule inhibitors in patients with advanced cancer


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Grace Tan1,Nadina Tinsley2,Cong Zhou1,Shaun Villa2,Paul Lorigan2,Fiona Blackhall2,Matthew Krebs2,Louise Carter2,Fiona Thistlethwaite2,Andrew Hughes1,Natalie Cook2
1University of Manchester,2Christie NHS Foundation Trust

Abstract

Background

Antibiotic use (ABX) has been shown to reduce the efficacy of immune checkpoint inhibitors (CKIs) in the treatment of cancer by eradication of the gut microbiome. The gut microbiome is known to be involved in the regulation of anti-tumour responses. Here, we determine if the a similar relationship exists between ABX use and small molecule inhibitors (SMIs) in patients with advanced cancer. 

Method

Retrospective data analysis was performed on metastatic cancer patients treated with SMIs at the Christie NHS Foundation Trust between January 2015 and March 2017. Patients with melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) patients were included. Patient demographics, prior treatments, extent of disease, SMI agent and use of antibiotics (route, duration, multiple ABX/successive courses) were collected. Progression free survival (PFS) and overall survival (OS) were compared between ABX+ (patients treated with ABX either 2 weeks before SMI initiation, or 6 weeks after) and ABX- groups (patients with no ABX within the specified timeframe). Statistical analyses were carried out with univariate and multivariate models.

Results

Of 261 patients, 69 (26%) received ABX of which the commonest were beta-lactams and quinolones. Multivariate analyses of ABX+ and ABX- groups found that no correlation exists between ABX use and PFS but ABX use was linked to shorter OS (median 490 days (ABX-) vs 309 days (ABX+)).

Conclusion

This is the first analysis investigating the impact of ABX on SMI therapeutic outcomes. The data demonstrated evidence of a link between ABX and shortened OS therefore further studies are warranted to fully evaluate the potential causative role of the gut microbiome in reduced treatment outcomes of SMIs as other forms of anti-cancer therapies.