Efficacy and Safety of Immunotherapy in Post-Operative Recurrent/Metastatic Non-Small Cell Lung Cancer and Impacts of Previous Thoracic Radiotherapy

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<h3>Purpose/Objective(s)</h3> Immunotherapy has shown benefits to survival in patients with advanced non-small-cell lung cancer (NSCLC). Radiotherapy-induced immune activation can promote immune response, while lymphopenia with it may reduce the benefits. This study aimed to assess effectiveness and toxicity of immunotherapy in recurrent/metastatic NSCLC patients who previously received radical surgery and the impacts of previous thoracic radiotherapy (RT) on them. <h3>Materials/Methods</h3> Patients at a single institution who underwent pulmonary lobectomy with systematic lymphadenectomy (2000.1.1-2021.7.2) for stage I-III NSCLC and received immunotherapy after progression with or without previously thoracic RT were identified. The clinical data of included patients were retrospectively analyzed. The primary outcome was post-immunotherapy progression-free survival (PFS). Secondary endpoints included disease control rate (DCR), overall response rate (ORR) and toxicity (treatment suspension caused by immune-related adverse effects). <h3>Results</h3> A total of 92 patients were enrolled in the final cohort. Median age of included patients was 60.5 years, 72.8% were men. 33.7% were diagnosed as squamous cell carcinoma and 45.7% were stage III. In total, 7(7.6%), 67(72.8%) and 26(28.3%) received neoadjuvant chemotherapy, adjuvant chemotherapy and thoracic radiotherapy before anti-PD-1/PD-L1 treatment. Median follow-up time was 43.8 months (range, 3.4-54.1 months). 94.6% patients were treated by PD-1 inhibitor. Immune checkpoint inhibitor was administered as first-, second-, third or beyond-line systematic treatments in 45.7%,28.3% and 26.1% patients. The median PFS was 9.03m (95%CI 5.04-13.03m) and 1y-PFS was 43.9%. Among 86 evaluable patients, the DCR and ORR was 83.7% (95%CI 75.8%-91.7%) and 23.3% (95%CI 14.1-32.4%). 9(9.8%) patients had treatment suspended due to immune-related adverse effects, and 4/9 had ICI rechallenge. Patients received RT had comparable mPFS with non-RT group (12.1m vs 8.4m, p=0.685) and similar rates of irAEs-caused ICI suspension (p=0.709) even with higher proportion of stage III patients (80.8% vs 31.8%, p<0.001). Among stage III patients, 50% received RT and had shown tendency of longer median PFS (12.1m vs 6.4m, p=0.107). <h3>Conclusion</h3> Immunotherapy shown considerable efficacy in stage I-III NSCLC patients after radical surgery and progression. Patients with previous thoracic RT shown non-inferior survival and similar toxicity, and had potential survival benefits in stage III subgroup.