8037 Background: Concurrent chemoradiotherapy followed by consolidation immunotherapy is the standard treatment for unresectable stage III LA-NSCLC; however, many patients in real-world practice are unable to complete concurrent therapy, and locoregional failure remains common. This phase II study evaluated induction chemoimmunotherapy followed by hypofractionated radiotherapy (hypo-RT) and consolidation immunotherapy to improve feasibility and disease control. Methods: Patients with newly diagnosed unresectable stage III NSCLC received 3-4 cycles of immune checkpoint inhibitors combined with platinum-based doublet chemotherapy. Patients without progression or grade ≥2 pneumonitis underwent eligibility assessment for hypo-RT based on anatomical suitability and organ-at-risk constraints. Eligible patients received definitive sequential hypo-RT (48–60 Gy in 12–15 fractions based on tumor regression) and consolidation immunotherapy when appropriate. The primary endpoint was progression-free survival (PFS) with secondary endpoints of safety and overall survival (OS). Results: Between October 2022 and October 2025, 132 patients received induction chemoimmunotherapy, and 55 underdoing hypo-RT. Median age was 70 years (range, 47–85), and 42 patients (76.4%) had squamous cell carcinoma. Programmed death-ligand 1 (PD-L1) expression ≥1% was observed in 17 patients (30.9%), with unknown PD-L1 status in 14 patients (25.5%). With a median follow-up of 20.1 (95%CI, 17.3-22.9) months, median PFS and OS were not reached. The 1- and 2-year PFS rates were 88.1% (95% CI, 78.8%–98.5%) and 58.5% (95% CI, 43.6%–77.7%), respectively; the 1- and 2-year OS rates were 100% and 77% (95% CI, 61.5%–93.7%), respectively. Isolated in-field recurrence occurred in 4 patients (7.3%). Pneumonitis was the most common acute nonhematologic toxicity, with grade 3 in 4 patients (7.3%) and grade 4 in 1 patient (1.8%). Grade 3 atelectasis occurred in 4 patients (7.3%), and grade 3 radiation esophagitis in 2 patients (3.6%). No grade 5 toxicities were observed. Conclusions: Induction chemoimmunotherapy followed by eligibility-adapted hypofractionated radiotherapy showed promising survival and locoregional control with acceptable toxicity in unresectable locally advanced NSCLC, supporting its feasibility as an alternative strategy for selected patients. Clinical trial information: NCT05784142 .
Zhu et al. (Thu,) studied this question.