Efficacy and safety of immunotherapy in real-world patients with advanced non-small cell lung cancer

OBJECTIVE: The aim of this study was to explore the predictors of immunotherapy efficacy for advanced non-small cell lung cancer (NSCLC) in the real world and to analyze the clinical efficacy and safety of patients receiving immunotherapy for advanced NSCLC. METHODS: Clinical pathological data from patients diagnosed with advanced NSCLC treated with immune checkpoint inhibitors (ICIs) were collected. Survival analysis and differential efficacy comparison of progression-free survival (PFS) was performed using the Kaplan-Meier method and Log-rank test. Univariate and multivariate analyses of PFS and objective response rate (ORR) were performed by Cox proportional risk regression models and logistic regression models to explore influence factors associated with the prognosis of immunotherapy. RESULTS: (1) Overall, the median PFS (median PFS, mPFS) for 237 patients was 11.3 months (range: 8.5-14.1), the ORR was 55.7 %. Univariate and multivariate analyses of PFS in the overall population found that age ≥65 years, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score of 0-1, clinical stage III, absence of liver metastases, immunotherapy combined with chemotherapy and prognostic nutritional index (PNI) ≥47.8 were independent predictors of longer PFS in immunotherapy-advanced NSCLC. Univariate and multifactorial logistic regression analysis of ORR in 237 patients suggested that ECOG PS score, number of ICI lines and prognostic nutritional index (PNI) were independent influence factors of ORR. (2) In the "stage IV, first-line, ECOG PS 0-1" subgroup, 106（106/237）patients had an mPFS of 10.9 months (range: 9.6-12.2) and an ORR of 59.4 %. Univariate and multivariate analyses of PFS in subgroups found that liver metastases, immunotherapy combined with chemotherapy and PNI were independent influencers of PFS. A univariate analysis of ORR found that only High-PNI was associated with longer PFS. (3) Additional factors affecting the efficacy were explored. A subgroup analysis among 64 (64/237) patients with accessible programmed death-ligand 1 (PD-L1) expression levels showed a trend towards a PFS benefit in patients with PD-L1 tumor cell proportion score (TPS) ≥ 50 % and TPS < 1 % compared to patients with PD-L1 TPS < 1 % (p=0.196); A subgroup analysis among 91 (91/237) patients with traceable genetic test results showed that patients with positive driver genes (KRAS/MET/RET/HER2/EGFR/ALK) had a shorter PFS than patients with negative driver genes (HR=1.712, 95 % CI: 0.994-2.947, p=0.048); Subgroup analyses of efficacy assessment showed significantly prolonged PFS in patients with an initial or best outcome assessment of complete response (CR) or partial remission (PR) compared with stable disease (SD) or progressive disease (PD) (P < 0.001). (4) Immune-related adverse events (irAEs) requiring pharmacological intervention or discontinuation were recorded. 61 (61/237) patients experienced irAEs during treatment. Grade 1∼2 adverse reactions occurred in 27.8 % of patients and grade ≥3 adverse reactions in 3.8 % of patients. There was no statistical difference in the occurrence (P=0.728) and severity (P=0.612) of adverse events between the ICIs. CONCLUSION: This study reports the practical experience of ICIs in the treatment of NSCLC in China by analyzing the efficacy and safety of real-world advanced NSCLC treated with ICIs. The results were generally consistent with those of clinical trials, and the factors with the greatest impact on the efficacy of ICIs were ECOG PS, clinical stage, and PNI. Therefore, physicians can predict the future benefit of immunotherapy for NSCLC based on clinical prognostic indicators and make individualized treatment choices.