Effect of antibiotic treatment on immune checkpoint inhibitors efficacy in patients with advanced non-small cell lung cancer

Abstract

BACKGROUND: Gut microbiotaplays a crucial role in immune response. Recent data have shown that antibiotic (ATB) usage influences efficacy of immune check point inhibitors (ICIs) via altering microbiota of the gut. METHODS: We retrospectively analyzed patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs as monotherapy or combination with chemotherapy (ChT) at the one academic center. Those receiving ATB for the first 12 weeks of the initiation of ICIs were compared with those who did not. The primary objective of this study was to assess the impact of ATB use on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) during ICIs therapy. RESULTS: 90 patients were included in our analysis. Of these 90 patients, 27 (30%) received ATB in the first 12 weeks of the treatment. In patients who received ATB in the first 12 weeks of ICIs administration, PFS was significantly shorter (4.9 vs. 24.8 months, HR 2.52, 95% CI (1.52-4.18), p < 0.001). OS was also significantly shorter (5.4 vs. 37.8 months, HR 2.55, 95% CI (1.48-4.40), p = 0.001). We also examined the impact of ATB on ORR. Exposure to ATB for the first weeks consistently worsened the response rate; the ORR was 25.9% in the ATB group and 55.6% in the no ATB group (p = 0.01). CONCLUSION: Our findings demonstrated that the use of antibiotics around ICIs initiation was associated with decreased OS, PFS, and ORR in patients with NSCLC. This suggests that microbiota diversity may be one of the factors predicting the efficacy of ICIs.