179 - Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT): Long-Term Outcomes

Materials/Methods: Key eligibility criteria for chemotherapy-free treatment in SPRINT included stage II-III NSCLC, ECOG performance status 0-1, and PD-L1 TPS = 50%. SPRINT participants were treated with three cycles of induction pembrolizumab, followed by a four-week course of personalized and deintensified radiotherapy (48 Gy for tumors and lymph nodes smaller than 20 cc after induction, 55 Gy for larger lesions), followed by up to 13 cycles of consolidation pembrolizumab. Progression-free survival (PFS) and overall survival (OS) outcomes were estimated using the Kaplan–Meier method, and adverse events (AE) and patterns of failure were reported using descriptive statistics.

Results: Between September 2018 and November 2021, 25 patients with LA-NSCLC and PD-L1 TPS = 50% were enrolled across three institutions. Most patients (n= 22, 88%) had stage IIIA or IIIB disease, and the median PD-L1 TPS was 75% (range 50-100%). The median follow-up duration is 58 months, and 12 patients (48%) have developed disease progression, most commonly in the chest (n=4) or in the brain (n=4). Progression-free survival and overall survival outcomes for the entire patient cohort and key subgroups are shown in the Table below. Favorable outcomes were observed in patients who demonstrated response on PET following induction immunotherapy (defined as >30% reduction of maximum SUV) and in cases with very high PD-L1 expression. PD-L1 expression was not associated with response on PET to induction immunotherapy. The SPRINT regimen remained well-tolerated—no new high-grade treatment-related toxicities have been observed since initial trial reports, and grade 3 toxicities were limited to two cases (8%) of diarrhea and single cases (4%) of anemia, arthritis, esophagitis, pneumonitis, and weight loss.

Conclusion: In patients with LA-NSCLC and PD-L1 TPS =50%, sequential immunotherapy and risk-adapted, deintensified radiotherapy yields excellent long-term outcomes. Response on PET to induction immunotherapy and high PD-L1 expression may be useful prognostic factors in this setting. The promising findings of this chemotherapy-free approach provide the foundation for ongoing trials using novel, biomarker-driven therapies for LA-NSCLC (NCT06865339).