2545 - Treatment Strategy for Potentially Resectable Stage III-N2 Driver Gene-Negative NSCLC in the Immunotherapy Era
Presenter(s)
J. Zhao1, K. Wang2, B. Huang1, M. Li1, X. Wang2, J. Zhu1, X. Meng1,3, and G. Cai1; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 2School of Clinical Medicine, Shandong Second Medical University, Weifang, China, 3School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Purpose/Objective(s): Stage III-N2 non–small cell lung cancer (NSCLC) is highly heterogeneous, and the optimal treatment regeimen for patients with potentially resectable III-N2 NSCLC is still unclear. This study aimed to compare the efficacy of three treatment strategies in patients with potentially resectable stage III-N2 NSCLC with negative driver genes: neoadjuvant chemoimmunotherapy followed by surgery (NCIT+Surgery), NCIT followed by concurrent chemoradiotherapy (NCIT+cCRT), and definitive cCRT followed by immunotherapy (cCRT+IT).
Materials/Methods: Patients with clinical stage III-N2 NSCLC at a single institution from 2019 to 2024 were retrospectively enrolled and were divided into NCIT+Surgery, NCIT+cCRT and cCRT+IT groups. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Subgroup analyses include metastatic N2 lymph node status (multi-station/bulky N2), clinical stage, PD-L1 expression level, radiographic response after NCIT, and adjuvant/consolidation immunotherapy after surgery or cCRT. One-to-one propensity score matching (PSM) was utilized to balance the baseline differences between NCIT+Surgery and NCIT+cCRT groups, NCIT+Surgery and cCRT+IT groups, and NCIT+cCRT and cCRT+IT groups. PFS and OS were evaluated using the Kaplan-Meier method, and the log-rank test was used for group differences.
Results: With a median follow-up of 31.7 months, a total of 304 patients were included and categorized into three groups: NCIT+Surgery (n=148), NCIT+cCRT (n=46), and cCRT+IT (n=110). Both before and after 1:1 PSM, NCIT+Surgery demonstrated significant PFS benefits and a trend towards improved OS compared to cCRT+IT. However, there were no significant differences in either PFS or OS between groups NCIT+Surgery and NCIT+cCRT. Subgroup analysis showed that after PSM, there was no significant difference in PFS and OS between NCIT+Surgery and cCRT+IT groups in patients with multi-station N2 metastasis or bulky N2 metastasis. However, among patients without multi-station N2 metastasis or bulky N2 metastasis, PFS and OS were significantly inferior in the cCRT+IT group compared to the NCIT+Surgery group. For other subgroup analyses, including clinical stage, PD-L1 expression level, radiographic response after NCIT, and adjuvant/consolidation immunotherapy after surgery or cCRT, the results were consistent with the overall analysis.
Conclusion: cCRT may be a viable alternative to surgery in patients with potentially resectable III-N2 NSCLC who do not undergo surgical resection after initial NCIT, offering comparable efficacy. For potentially resectable NSCLC patients with multi-station N2 or bulky N2 metastasis, definitive cCRT+IT may also be a viable treatment option. Larger prospective studies are needed to validate these findings and optimize the treatment strategies for this patient population.