Safety and Efficacy of Radiotherapy Combined With Sintilimab in Advanced NSCLC Patients Who Progressed on First or Second Line Therapy: A Prospective, Multiple Center, and Single‐Arm Study

ABSTRACT Background This study explored the safety and efficacy of combining radiotherapy with sintilimab in non‐small cell lung cancer (NSCLC) patients who have progressed after first or second‐line therapy. Methods In this multicenter, single‐arm trial, patients with NSCLC who had progressed after first or second‐line therapy were enrolled. Participants received hypofractionated stereotactic body radiotherapy (SBRT) (requiring a single‐site biological dose of more than 30 Gy or planned to reach 30 Gy) followed by sintilimab every 3 weeks until disease progression or unacceptable toxicity occurred. Results From March 1, 2019, to July 27, 2023, 14 patients were enrolled across two centers. The cohort included 64.3% males and 35.7% females, with a median age of 67 years (range 57–73 years). All participants completed radiation therapy and received at least one cycle of sintilimab. The overall response rate (ORR) was 21.4% (3/14) and the disease control rate (DCR) was 71.4% (10/14). The absent radiation response (ARR) was 14.3% (2/14). The median PFS was 4.17 months (95% CI: 1.15–8.69 months), with a 6‐month PFS rate of 42.9%. The median OS was 16.17 months (95% CI: 11.69–20.64 months). Overall, 10 patients (71.4%) experienced at least one treatment‐emergent adverse event (TEAE). Grade 3 adverse events included one case each of immune‐related myocarditis, thrombocytopenia, and checkpoint inhibitor pneumonitis (CIP). Four patients (28.6%) had immune‐related adverse events (irAEs) including skin rash and pruritus (2/14, grade 1), immune‐related myocarditis (1/14, grade 3), and CIP (1/14, grade 3). Conclusions Radiotherapy combined with sintilimab for NSCLC patients who progressed after first‐or second‐line therapy showed promising efficacy outcomes.