1466P - Gut microbiota mediates the protective effects of postbiotics attenuating the immune-related adverse events in non-small-cell lung cancer patients: A randomized, controlled trial in Chongqing, China

Background

To evaluate the effects of JK5G postbiotics on regulating the imbalanced gut microbiota and its impacts on the efficacy and incidence rate of immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).

Methods

We conducted a randomized, controlled trial in China and included non-squamous or squamous NSCLC patients without EGFR, ROS1, and ALK alteration, stage IIIb-IV. Patients were randomly (1:1) divided into two groups to receive four cycles of programmed cell death-1 (PD-1) plus chemotherapy plus placebo (control group) or to receive PD-1 plus chemotherapy plus JK5G postbiotics (JK5G group). The primary endpoint were adverse effects, quality of life (QoL), 16S DNA sequencing of gut microbiota, blood inflammatory cytokines, and lymphocyte subsets. This study was registered at www.chictr.org.cn (ChiCTR2200064690).

Results

60 patients were enrolled. The JK5G group had better QoL and nutritional levels, as well as lower depression symptoms than the control group (all p < 0.05). The JK5G group had a lower incidence of anemia (55.56% vs. 11.11%, p = 0.012), decreased lymphocyte count (33.33% vs. 0%, p = 0.019), decreased appetite (55.56% vs. 16.67%, p = 0.035), nausea (55.56% vs. 11.11%, p = 0.012), and asthenia (50.00% vs. 11.11%, p = 0.034) than the control group. Moreover, JK5G attenuated intestinal flora imbalance, accompanied by increased Faecalibacterium, Ruminococcaceae, and fecal butyrate concentration. Furthermore, JK5G administration significantly decreased the pro-inflammatory markers, including TNF-α, IL-2, and C-reactive protein (CRP) (p < 0.05). Significant increases in CD3+CD4+ T cells and CD4/CD8 ratio were observed in the peripheral blood of JK5G group patients (p < 0.05).

Conclusions

Our current findings indicated that JK5G postbiotics may attenuated irAEs, enhanced the QoL and nutrition levels in advanced NSCLC patients who received ICIs. JK5G postbiotics could improve the gut microbiota structures and accompanied with the ameliorate of tumor microenvironment and inflammation.

Clinical trial identification

ChiCTR2200064690.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.