Induction Immunochemotherapy Followed by Definitive Chemoradiotherapy for Unresectable Locally Advanced Non-Small Cell Lung Cancer

Abstract

Concurrent chemoradiotherapy (cCRT) followed by immune checkpoint inhibitors (ICIs) consolidation is the current standard of care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, most patients diagnosed with unresectable LA-NSCLC will not meet the criteria for adjuvant ICIs in the real world. Theoretically, adjusting the ICIs from the consolidation phase to the induction setting could greatly improve the patient' s compliance to receive ICIs therapy. Consequently, we performed this study to evaluate the efficacy and safety of induction ICIs and chemotherapy followed by definitive CRT for unresectable LA-NSCLC. A total of 102 unresectable stage III NSCLC patients who received neoadjuvant immunochemotherapy followed by definitive CRT between 2019 and 2022 were identified. The primary endpoint of this study was to determine the efficacy of this treatment pattern, including overall survival (OS) and progression free survival (PFS). Disease control rate (DCR) and toxicities were the secondary objective. The median age was 64 years (range 34-81), including 58 (56.9%) squamous cell carcinoma and 37 (36.3%) non-squamous cell carcinoma patients. There were 34 (33.3%), 39 (38.2%) and 29 (28.4%) patients with stage IIIA, IIIB and IIIC disease, respectively. The DCR at the end of induction immunochemotherapy was 87.3%. The median PFS was 20.4 months (95% CI, 15.7-25.1), with PFS rates of 90.1% at 6 months, 70.4% at 1 year, 55.2% at 18 months and 41.9% at 2 years. The rates of OS were 92.8%, and 76.2% at 1 year, and 2 years, respectively, and the median OS was not reached. For patients without progression before CRT, the median OS was also not reached, and the median PFS was 21.3 months. Patients receiving concurrent CRT manifested significantly better OS, compared with sequential CRT (12-month OS, 89.4% vs. 100.0%; 24-month OS, 70.2% vs. 87.3%; P = 0.030). Patients with PD-L1 expression of 50% or more manifested significantly higher partial response rate (70.4% vs. 45.3%, P = 0.033), along with better survival (median PFS, 17.3 months vs. NR, P = 0.034; median OS, 26.5 months vs. NR, P = 0.037), compared to those less than 50%. Treatment was well tolerated, with an incidence of 4.9% for grade 3 or greater pneumonitis or radiation pneumonitis (RP). The most common severe (grade ≥3) adverse events were hematologic toxicities and no unexpected treatment related toxicities occurred. Induction immunochemotherapy followed by definitive CRT showed promising efficacy and tolerable toxicities for unresectable LA-NSCLC, especially for those with tumoral PD-L1 expression over 50%.