Gegen Qinlian Tablets attenuate immune-related adverse events in NSCLC patients: A multi-center randomized controlled trial in China

Background: Immune related adverse events (irAEs) significantly compromise patients' quality of life and limit the application of immunotherapy. Gegen Qinlian Tablets (GQT), a classical Chinese herbal formula, have shown potential in mitigating irAEs. However, clinical evidence supporting the use of GQT as a synergy therapy for immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC) remains insufficient. Purpose: To evaluate the efficacy and safety of GQT in reducing the incidence of irAEs in NSCLC with ICI treatment. Study design: A multi-center, open-label, randomized controlled trial. Methods: Eligible patients were randomly assigned (1:1) to receive ICI plus chemotherapy plus GQT (GQT group) or ICI plus chemotherapy alone (control group). The primary outcome was the incidence and severity of irAEs. Secondary outcomes included objective response rate (ORR) and disease control rate (DCR). Serum levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were assessed at baseline and after treatment. Results: From October 2022 to August 2024, 94 participants were randomized to the GQT group (n = 47) or the control group (n = 47) at four hospitals in China. The incidence of irAEs was significantly lower in the GQT group than in the control group [31.91 % (15/47) vs. 59.57 % (28/47), p = 0.007, 95 % CI: 0.137-0.741]. No patient in the GQT group experienced multi-systemic toxicity, whereas 3 patients in the control group did (3/28, 10.7 %). The median onset time of irAEs in the GQT group was 14.9 weeks, and was 8.7 weeks in the control group (p = 0.807). Among response-evaluable patients, the ORR was 48.9 % (0 CR, 23 PR) in the GQT group (n = 45), and 36.2 % (1 CR, 16 PR) in the control group (n = 43) (p = 0.211, 95 % CI: 0.686-3.725). IL-6 level significantly decreased after 3 treatment cycles in the GQT group (p < 0.001), potentially contributing to the reduced incidence of irAEs. Conclusion: GQT significantly reduced the incidence of irAEs and prolonged the median onset time of irAEs in patients with advanced NSCLC receiving ICI therapy. The observed effects may be associated with the downregulation of IL-6. GQT showed promise as a synergistic treatment that mitigated irAEs and might enhance the therapeutic efficacy of ICIs.