H. Liu1, X. Gan1, W. Xie1, L. Zhang2, X. Sun1, Q. Xiao2, and H. Wang3; 1Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China, 2Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China, 3Department of Radiation Oncology, Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
Purpose/Objective(s): This is a retrospective study which aims to compare the differences in efficacy and toxicity between unresectable stage III non-small-cell lung cancer (NSCLC) patients treated with definitive radiotherapy plus induction or consolidation immune checkpoint inhibitors (ICIs). Materials/
Methods: A retrospective analysis was conducted on patients who underwent definitive radiotherapy combined with induction or consolidation ICIs from November 2019 to October 2022. The patients were divided into the induction ICIs with chemotherapy (iICIs) and consolidation ICIs (cICIs) group. The survival outcomes and toxicity were compared among these groups. Additionally, the study aimed to identify predictive markers of the efficacy of induction ICIs. Results: This study included 169 patients for analysis, with 111 in the iICIs and 58 in the cICIs group. The baseline characteristics were well-balanced between the two groups. Notably, the iICIs group exhibited a significantly improved median PFS compared to the cICIs group (35.6 vs. 22.1 m, P = 0.03). However, the median overall survival (OS) and the incidence of grade 3 or higher pneumonitis were similar between the two groups (45.5 vs. 42.8 m, P = 0.575; 3.6% vs. 5.2%, P = 0.69, respectively). No significant disparities were observed in survival outcomes and adverse events in patients from the iICIs group, whether they received consolidation ICIs or not. In the iICIs group, pre-treatment neutrophil lymphocyte ratio (NLR) <4.93 was associated with significantly better PFS (35.6 vs. 16.3 m, P=0.022) and OS (HR=0.28, 95% CI: 0.1-0.82, P=0.02) compared to NLR =4.93. Similarly, patients with pre-treatment prognostic nutritional index (PNI) <50.38 exhibited a PFS benefit compared to those with PNI =50.38 (HR=0.4, 95% CI: 0.18-0.88, P=0.023), while no significant difference was observed in OS (P=0.268). Pre-treatment platelet lymphocyte ratio (PLR) <170.14 or not did not show significant differences in PFS or OS. Multivariate COX regression analyses identified pre-treatment NLR and PNI as independent predictors of PFS in the iICIs group. Those who with NLR <4.93 and PNI <50.38 in the iICIs group demonstrated significantly better PFS (HR=0.15, 95% CI: 0.04-0.51, P=0.002) and OS (HR=0.22, 95% CI: 0.05-0.94, P=0.042) than others. And these patients showed a significant better PFS (HR=0.14, 95% CI: 0.04-0.5, P=0.003) compared to patients in the cICIs group, with no significant difference in OS (P=0.275). Conversely, patients in the iICIs group with NLR >4.93 or PNI >50.38 exhibited similar PFS and OS compared to the cICIs group. Conclusion: The findings of this study indicate that induction ICIs for stage III unresectable NSCLC treated with definitive radiotherapy resulted in a significant improvement in PFS compared to consolidation ICIs, without a notable increase in the incidence of adverse events. Moreover, pre-treatment NLR and PNI could serve as biomarkers to identify individuals who would benefit from induction ICIs.
