Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non–Small Cell Lung Cancer

Many patients with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy show primary resistance. High-dose radiotherapy can lead to increased tumor antigen release, improved antigen presentation, and T-cell infiltration. This radiotherapy may enhance the effects of checkpoint inhibition.

To assess whether stereotactic body radiotherapy on a single tumor site preceding pembrolizumab treatment enhances tumor response in patients with metastatic NSCLC. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized phase 2 study (PEMBRO-RT) of 92 patients with advanced NSCLC enrolled between July 1, 2015, and March 31, 2018, regardless of programmed death-ligand 1 (PD-L1) status. Data analysis was of the intention-to-treat population. INTERVENTIONS: Pembrolizumab (200 mg/kg every 3 weeks) either alone (control arm) or after radiotherapy (3 doses of 8 Gy) (experimental arm) to a single tumor site until confirmed radiographic progression, unacceptable toxic effects, investigator decision, patient withdrawal of consent, or a maximum of 24 months. MAIN OUTCOMES AND MEASURES: Improvement in overall response rate (ORR) at 12 weeks from 20% in the control arm to 50% in the experimental arm with P