Association between the efficacy and immune-related adverse events of pembrolizumab and chemotherapy in non-small cell lung cancer patients: a retrospective study

Background The combination of immune-checkpoint inhibitors with chemotherapy has become the standard of treatment for non-small cell lung cancer (NSCLC) patients. However, the association between therapeutic efficacy and the development of immune-related adverse events (irAEs) remains unclear in patients treated with combination therapy. We aimed to investigate the frequency of irAEs, and the association between therapeutic efficacy and the development of irAEs in patients with NSCLC. Materials and methods We retrospectively surveyed patients with chemo-naïve advanced NSCLC who received pembrolizumab plus platinum-based chemotherapy or pembrolizumab monotherapy at Juntendo University Hospital, Japan, between February 2017 and May 2021. Results Among 148 patients (median [range] age, 68 (33-85) years; 107 men [72.3%] and 41 women [27.7%]), 74 each received pembrolizumab plus chemotherapy and pembrolizumab monotherapy. IrAEs were observed in 46 (62.2%) and 41 patients (55.4%) in the combination therapy and monotherapy group, respectively. Patients with irAEs showed significantly longer progression-free survival (PFS) than those without irAEs in the combination therapy group (8.9 vs. 5.7 months; Hazard Ratio [HR], 0.53; 95% CI, 0.29-0.98; P = 0.041) and monotherapy group (11.7 vs. 5.0 months; HR, 0.40; 95% CI, 0.22-0.70; P = 0.001). In the multivariable analysis, development of irAEs was positively associated with PFS in both the groups (HR, 0.48; 95% CI, 0.26-0.89; P = 0.019 and HR, 0.38; 95% CI, 0.21-0.68; P < 0.01). In the inverse probability of treatment weighting adjusted analysis, development of irAEs was significantly associated with combination therapy (OR, 0.56; 95% CI, 0.34-0.91; P = 0.019). Conclusion Our study demonstrated that the incidence of irAEs was associated with favorable efficacy in patients treated with pembrolizumab plus chemotherapy, as well as pembrolizumab monotherapy. Also, the addition of chemotherapy to pembrolizumab significantly increased the incidence of irAEs. Keywords: Non-small cell lung cancer, Immune-checkpoint inhibitors, Combination therapy, Immune-related adverse events