Effect of antimicrobial therapy on progression-free survival of patients with non-small cell lung cancer receiving checkpoint inhibitor- and chemotherapy.

Abstract

Checkpoint inhibitor therapy (CPI) has significantly changed therapy in non-small cell lung cancer (NSCLC) in recent years. There are some data that the effect of CPI therapy is influenced by the microbiome. Little is known about the influence and timing of antimicrobial therapy (AMT) on the microbiome-mediated effect on CPI therapy. We retrospectively analysed 70 patients (age 68 ± 9.2 years) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab) or chemotherapy (platin doublet or docetaxel/nintedanib or pemetrexed). We registered patient's characteristics including presence and timing of AMT. Group 1 consisted of 27 patients with AMT in the month before CPI- or chemotherapy, group 2 was 30 patients with AMT during CPI- or chemotherapy, and group 3 was 43 patients without AMT. Groups 1-3 showed comparable patient characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression-free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.56 vs. 5 ± 0.99, p = 0.005, 95% CI: 0.13-0.67). In patients, who were treated with chemotherapy alone, there was no difference in PFS in those with or without AMT in the month before therapy (5 ± 0.99 vs. 6 ± 0.81months, p = 0.3). Interestingly, AMT during chemotherapy or CPI therapy showed no effect on PFS. In a real-life setting, we found that AMT reduces PFS when given in the month before CPI therapy. AMT before chemotherapy and during CPI and chemotherapy seems not to influence PFS. The best PFS was seen in patients without AMT before CPI therapy. This implies the need for an even more restrictive use of AMT in the context of patients with NSCLC stage IV disease.