Antibiotic Usage Reduced Overall Survival by over 70% in Non-small Cell Lung Cancer Patients on Anti-PD-1 Immunotherapy

Abstract

Background/Aim: There is an increasing use of immunotherapy for non-small cell lung cancer (NSCLC) patients. The present study analysed the effect of antibiotic use on the outcome of NSCLC patients undergoing treatment with anti-programmed cell death-1 (anti-PD-1) immunotherapy. Patients and Methods: This was a retrospective study of 69 NSCLC patients. Eighteen out of 69 patients received antibiotics within 21 days before or within 21 days after start of anti-PD-1 therapy. Results: Patients treated with anti-PD-1 antibodies receiving antibiotics had greatly decreased objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) compared to those who did not use antibiotics. Multivariate analysis showed that antibiotic treatment of patients on anti-PD-1 antibody therapy was an independent negative predictive factor of PFS; however, it was not a significant independent predictive factor of OS. Conclusion: Use of antibiotics within 21 days before and after anti-PD-1 treatment initiation in patients with NSCLC strongly reduced OS and PFS, suggesting the two treatments should not be combined.Immunotherapy with anti-programmed cell death-1 (anti-PD-1) antibody has been only modestly successful in non-small cell lung cancer (NSCLC) (1). Thus, there is a critical need to identify more effective treatment strategies for anti PD-1 treatment of NSCLC.Specific intestinal bacteria have been reported to affect the immune system and therapeutic outcome of anti-PD-1 immunotherapy in NSCLC, melanoma, renal cell carcinoma (RCC) and urothelial carcinoma (UC) (2-5). Additionally, the diversity of bacterial flora may also affect the therapeutic outcome of anti-PD-1 immunotherapy (6).

Effects of Concomitant Antibiotics Use on Immune Checkpoint Inhibitor Efficacy in Cancer Patients

“…Through database retrieval, 81 relevant literatures were obtained, including 8 Chinese literatures, 73 English literatures, 23 conference papers and abstracts, and 67 duplicated literatures, case reports, reviews and irrelevant contents were excluded. 37 literatures were screened strictly in accordance with the above screening process, and finally 12 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) studies were included in the quantitative analysis. A total of 6010 cancer patients were involved, of whom 1414 were treated with ABX in the treatment window of ICIs, as shown in Figure 1.…”

Intratumoral Microbiota Impacts the First-Line Treatment Efficacy and Survival in Non-Small Cell Lung Cancer Patients Free of Lung Infection

“…Also, the analysis of T cells and B cells implied that these bacteria in the lung may change the immune cell infiltration in LC tissues. Recently, a retrospective study of 69 NSCLC reported that patients treated with anti-PD-1 antibodies receiving antibiotics had greatly decreased objective response rate, OS, and PFS compared to those who did not use antibiotics [ 18 ]. This result highlights that inappropriate usage of antibiotics may influence the flora of the tumor environment and impair the treatment effect.…”

Emerging Immune-Monitoring System for Immune Checkpoint Inhibitors

“…We compared NSCLC patients receiving anti-PD-1 antibody treatment with and without antibiotics and found that both the PFS and overall survival (OS) were significantly lower in the group that used some antibiotics within 3 weeks before and after the start of anti-PD-1 antibody treatment than those in the group that did not use antibiotics. In other words, antibiotic use hampers the efficacy of ICIs [ 70 ]. Using antibiotics is known to cause dysbiosis of the gut microbiota [ 71 ], suggesting that dysbiosis could reduce the efficacy of PD-1 antibody therapy.…”