Antibiotics, PPIs may adversely affect immunotherapy outcomes
medwireNews: Individuals receiving atezolizumab for advanced non-small-cell lung cancer (NSCLC) may have worse survival if they are also taking antibiotics or proton pump inhibitors (PPIs), indicates an analysis of the POPLAR and OAK trials.
Whether co-medication with antibiotics and PPIs is “purely prognostic or contributing to resistance to checkpoint inhibition remains a matter of debate,” say the study authors.
“However, these data should encourage physicians to carefully evaluate the need for co-medications such as PPI and [antibiotics] in their patients,” they add.
For this exploratory analysis, Myriam Chalabi, from the Netherlands Cancer Institute in Amsterdam, and colleagues used data from the phase 2 POPLAR and phase 3 OAK trials in which patients with previously treated NSCLC were randomly assigned to receive either atezolizumab or docetaxel, with a view to evaluating overall survival (OS) as the primary endpoint.
In all, 22.3% of the 757 patients in the atezolizumab group were prescribed antibiotics in the 30 days before or after initiating treatment, as were 26.8% of the 755 patients in the docetaxel group. The rates of PPI use were 30.9% and 34.4%, respectively, and 9.8% and 10.9% used both classes of medication.
OS analysis of the total cohort showed a significantly higher risk for death with the use of antibiotics or PPIs, with hazard ratios (HRs) of 1.20 and 1.26, respectively, after multivariate adjustment.
However, when the treatment groups were analyzed separately, the findings were statistically significant in the atezolizumab, but not docetaxel, group.
Specifically, median OS was significantly shorter for atezolizumab-treated patients who also received antibiotics or PPIs than those who did not, at 8.5 versus 14.1 months (HR=1.32) and 9.6 versus 14.5 months (HR=1.45), respectively. There was also a significant correlation between PPIs and worse progression-free survival in the atezolizumab group, with median durations of 1.9 and 2.8 months for use versus no use (HR=1.30), respectively.
Although the associations between antibiotic or PPI use and OS were not significant among docetaxel-treated patients, the HRs were above 1 and an effect of these co-medications on chemotherapy outcomes “cannot be ruled out,” say Chalabi and colleagues in the Annals of Oncology.
Noting that recent research has pointed to an effect of the gut microbiome on immune checkpoint inhibitor (ICI) efficacy, the authors postulate that the gut dysbiosis induced by antibiotics and PPIs could explain the adverse associations identified in their study.
Chalabi et al stress the need for validation of these findings “in other independent datasets […] before our results can affect clinical decision-making,” and conclude: “Future research should focus on elucidating the possible mechanisms for interactions of ICI with co-medications, and the role of the microbiome.”
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