Phase 2 Trial of Combination Radiotherapy and Pembrolizumab Plus Chemotherapy in Patients With Previously Untreated Metastatic NSCLC: NJLCG 1902.

Introduction: Treatment strategies that enhance the efficacy of immunotherapy are desired. Radiotherapy can enhance immunity, but the utility of adding radiotherapy to immunotherapy plus platinum-doubled chemotherapy in patients with metastatic NSCLC has not been explored. Methods: This multicenter, single-arm phase 2 trial evaluated the efficacy and safety of combining radiotherapy with pembrolizumab plus chemotherapy in patients with previously untreated metastatic NSCLC. Patients begin receiving pembrolizumab plus platinum-doublet chemotherapy within 1 week of starting radiotherapy (30 Gy in 10 fractions). The primary end point was the 12-month progression-free survival (PFS) rate. The secondary end points included PFS, overall survival, and toxicity profiles. Results: Forty patients were enrolled. In total, 37 and 38 patients were analyzed for efficacy and safety, respectively. The 12-month PFS rate was 44.3% (90% confidence interval [CI]: 30.3-57.3), which met the primary end point. The median PFS was 8.4 months (95% CI: 5.7-22.2), and the median overall survival was 30.1 months (95% CI: 22.3-not reached). Grade 3 or 4 adverse events occurred in 25 patients (65.8%), and one treatment-related death was reported. Pneumonitis was reported in 10 patients (26.3%), including two cases of grade 3 pneumonitis and one case of grade 5. Conclusions: Adding radiotherapy to pembrolizumab plus platinum-doublet chemotherapy led to promising efficacy in patients with previously untreated metastatic NSCLC. Although caution should be exercised with regard to pneumonitis, adverse events were tolerable. Further research is needed to confirm the efficacy and safety of this strategy.