December 2, 2022

Do antibiotics affect the results of immunotherapy in lung cancer?


Antibiotic exposure is associated with inferior immune checkpoint inhibitor (ICI) treatment outcomes in patients with non-small cell lung cancer (NSCLC), according to a meta-analysis presented in the Society for Immunotherapy of Cancer (SITC) 2021 annual meeting.1

Previous studies have suggested that the gut microbiota may modulate the response to IBI. For example, tumor-bearing mice responded more favorably to ICI treatment when colonized with feces from malignant melanoma patients who responded to ICI treatment, compared to feces from non-responders.2

In clinical studies, exposure to antibiotics leading to microbiome dysbiosis negatively influenced the outcome of cancer patients treated with ICI, particularly those with NSCLC.3 However, most studies have been carried out retrospectively and have involved a small number of patients.

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With that in mind, Athena Crespin, of Da Volterra in Paris, and her colleagues conducted a meta-analysis to investigate the association between antibiotic use and outcome in NSCLC patients treated with IBI.

The researchers had already published their results in 2020.4 At SITC 2021, Ms. Crespin presented updated data encompassing studies published in journals or presented at conferences through September 2021.1

Study details and results

The meta-analysis included studies that reported a risk ratio or Kaplan-Meier curve for overall survival (OS) or progression-free survival (PFS) based on antibiotic exposure and / or data on response to treatment, such as objective response rate (ORR) and progressive disease rate (PD) based on exposure to antibiotics.

There were 36 studies involving 12,304 patients that included OS data and 29 studies involving 5,425 patients that included PFS data.

In these studies, patients treated with IBI who were exposed to antibiotics had significantly worse OS and PFS. The pooled risk ratios were 1.64 for OS (95% CI, 1.38-1.94) and 1.52 for PFS (95% CI, 1.29 to 1.80).

Approximately 51% of patients in the OS analysis received antibiotics within 2 months of starting ICI treatment (n = 6244) and 64% received antibiotics within 2 months of starting or starting treatment by ICI (n = 7859).

The risk ratios for OS were significantly worse for patients who received antibiotics during these 2 time windows, compared to patients who received no antibiotics at all or for patients who received antibiotics outside of these time windows.

There were 11 studies involving 2,061 patients that included FIT data and 11 studies involving 1,341 patients that included PD data. The odds ratios for ORR and PD were 0.60 (95% CI, 0.37-0.95) and 1.99 (95% CI, 1.45-2.7), respectively .

These were both statistically significant, reflecting a decreased chance of response to treatment and an almost 2-fold higher likelihood of PD in patients with NSCLC treated with IBI and exposed to antibiotics.