Magnetic resonance-guided split-course hypo-fractionated radiotherapy with concurrent chemotherapy and consolidative immunotherapy in locally advanced non-small cell lung cancer: A single arm, phase 2 study.

Abstract

To evaluate the efficacy and safety of magnetic resonance (MR)-guided split-course hypo-fractionated radiotherapy (hypo-RT) with concurrent chemotherapy followed by consolidative immunotherapy (CIT) in locally advanced non-small cell lung cancer (LA-NSCLC). In this phase 2 trial, patients with unresectable stage IIIA-C NSCLC (18-75 years old, Eastern Cooperative Oncology Group 0-1) received MR-guided split-course hypo-RT (30 Gy in six fractions, repeated after 4 weeks for a total of 60 Gy) with concurrent weekly docetaxel (25 mg/m²) and cisplatin (25 mg/m²). The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), objective response rate (ORR), and toxicities. Between July 2020 and January 2023, 104 patients were enrolled with a median follow-up of 34.4 months. Split-course hypo-concurrent chemoradiotherapy (CCRT) was completed in 101 (97.1%) patients, and 74 (71.2%) received CIT. The median PFS was 27.5 months (95% confidence interval [CI], 18.9-36.0 months), and the 1- and 2-year PFS rates were 76.9% (95% CI, 69.2%-85.5%) and 54.7% (95% CI, 45.9%-65.1%), respectively. The 1- and 2-year OS were 87.5% (95% CI, 81.4%-94.1%) and 65.3% (95% CI, 56.8%-75.2%), respectively. The most common grade 3-4 adverse event was lymphopenia (35.6%). Grade 2-3 pneumonitis was observed in eight patients (7.7%) during hypo-CCRT and in seven patients (6.7%) during CIT. Grade 3 esophagitis occurred in three patients (2.8%), and one grade 5 hemoptysis was reported (0.9%). The MR-guided split-course hypo-CCRT delivered at 5 Gy per fraction to a total dose of 60 Gy followed by CIT yielded encouraging survival outcomes with manageable toxicities in patients with LA-NSCLC.