Efficacy and safety of Gegen Qinlian tablets in attenuating immune-related adverse events in NSCLC patients: A randomized controlled, multicenter, open-label trial in China.

e20592 Background: Immune-related adverse events (irAEs) with high incidence are significant challenges, as they often lead to the interruption or discontinuation of immune checkpoint inhibitor (ICI) therapy. There is an urgent need for adjuvant therapies to mitigate irAEs. Here, we aimed to evaluate the efficacy and safety of Gegen Qinlian Tablets(GQT) in attenuating irAEs in non-small-cell lung cancer (NSCLC) patients treated with ICIs. Methods: In this randomized, multicenter, open-label trial, eligible patients with NSCLC at the first-line therapy were randomly (1:1) divided into two groups to receive ICI and chemotherapy (control group, n = 47) or to receive ICI and chemotherapy plus Gegen Qinlian Tablets (GQT group, n = 47). The primary endpoint was the incidence and severity of irAEs. The secondary endpoints included objective response rate (ORR) by RECIST v1.1. Exploratory indicators were the analysis results of 16s rRNA and metabolomics detection of fecal samples from GQT and control groups before initial treatment (T-P group, C-P group) and after 3 cycles of treatment (T-A group, C-A group). This study was registered at ClinicalTrials.gov (ChiCTR2200062607). Results: A total of 94 patients were enrolled from October, 2022 to July, 2024. The incidence of irAEs was 31.91% (15/47) in the GQT group and 59.57% (28/47) in the control group. The incidence of irAEs in the GQT group was decreased significantly (P = 0.007). No patient occurred multisystemic toxicity in the GQT group and 3 patients in the control group(3/28, 10.7%). The median onset time of irAEs in the GQT group was 14.9 weeks, and in the control group was 8.7 weeks (P = 0.807). The ORR was 48.9% (0 CR, 48.9% PR) among response-evaluable patients in the GQT group (n = 45), while it was 36.2% (2.1% CR, 34.0% PR) in the control group (n = 43) ( P = 0.211). 5 patients (10.6%) experienced constipation after receiving GQT. No other adverse reactions were attributed to GQT. The results of 16s rRNA and metabolomics detection of fecal samples showed significant differences in the gut microbiota composition between the T-P and T-A groups (P = 0.019). Compared to C-A patients, Subdoligranulum and Atopobiaceae were increased in T-A patients, while Holdemanella , Atopobium , and Escherichia_Shigella were significantly reduced. Furthermore, prostaglandin A1 was higher, while glyceric acid and deoxyadenosine were lower in the T-A compared with the C-A. And these metabolisms were found to be significantly enriched in glycerolipid metabolism and pentose phosphate pathway. Conclusions: Our current findings indicated that GQT might attenuate irAEs significantly and prolong the median onset time of irAEs by regulating the gut microflora and metabolites. GQT combined ICI plus chemotherapy could also improve the efficacy in first-line treatment of advanced NSCLC. Clinical trial information: ChiCTR2200062607 .