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Impact of antibiotic use and other concomitant medications on the efficacy of immune checkpoint inhibitors in patients with advanced cancer

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Abstract

Purpose

Recent evidences support a role of gut microbiota in influencing the efficacy of immune checkpoint inhibitors (ICI). The use of antibiotics (ATB) and other concomitant medications may impair the balance of microbiota and negatively affect the efficacy of immunotherapy.

Methods

Retrospective data analysis was performed on advanced cancer patients treated with ICI. Those receiving ATB within 4 weeks before or after initiating ICI were compared with those who did not. Likewise, those who received ATB (irrespective of time of onset) were compared with not exposed and was calculated the variable “ATB exposure” (AE) defined as the % “days of ATB/days of ICI”. Use of proton pump inhibitors (PPIs), opioids and steroids was also evaluated.

Results

Of the 102 patients included, 60 (58.8%) received ATB during immunotherapy treatment (ATB+ group), and 33 (32.3%) received them between 4 weeks before or after starting ICI (ATB4+ group). Median AE of the ATB-treated patients was 11.1% (range 5.6–21.3). PFS and OS did not differ between ATB4+ and ATB4− group or between ATB+ group and not treated one. However, both PFS and OS were significantly lower in patients with a higher AE than the median one (3.1 vs. 8.2 months, p = 0.007; 9.4 vs. 17.8 months, p = 0.02, respectively). PPIs or steroids use did not affect clinical outcome of ICI but opioids use was significantly associated with lower PFS and OS (4.5 vs. 8.1 months, p = 0.010; 8.6 vs. 26.3 months, p < 0.001, respectively).

Conclusions

Cumulative ATB use, rather than simple use in a defined time frame, may impair the efficacy of immunotherapy. Opioids use was also associated with poorer outcomes in patients treated with ICI.

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Abbreviations

AE:

Antibiotic exposure

ATB:

Antibiotics

ICI:

Immune checkpoint inhibitors

PPIs:

Proton pump inhibitors

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Acknowledgements

The author would like to thank Dr. Manuel Cobo Dols (Medical Oncology Department, Hospital Regional Universitario Málaga and IBIMA, Spain) for his suggestions on study protocol preparation and data collection and Andrés Blanco Hortas (Epidemiology Department, FIDIS, Hospital Lucus Augusti, Lugo, Spain) for his statistical help.

Funding

This research did not received any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Oncology Pharmacy Department, Hospital Universitario Lucus Augusti, Ulises Romero nº1, 27003, Lugo, Spain

    A. Iglesias-Santamaría

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  1. A. Iglesias-Santamaría
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Correspondence to A. Iglesias-Santamaría.

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Ethical approval

The study protocol was approved by the Ethic Committee for Investigation with medicinal products of Galicia (Ref 2019/099) and has been performed in accordance with the ethical standards laid down in the Declaration of Helsinki and its later amendments.

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Due to the retrospective nature of the study, written informed consent was not required. This paper does not contain any individual person’s data in any form.

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Iglesias-Santamaría, A. Impact of antibiotic use and other concomitant medications on the efficacy of immune checkpoint inhibitors in patients with advanced cancer. Clin Transl Oncol 22, 1481–1490 (2020). https://doi.org/10.1007/s12094-019-02282-w

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