Theelen WSME, et al. - In patients with metastatic non–small cell lung cancer (NSCLC), researchers ascertained if stereotactic body radiotherapy on a single tumor site preceding pembrolizumab (200 mg/kg every 3 weeks) treatment enhances tumor response. Data reported that the overall response rate (ORR) at 12 weeks was 18% in the control arm compared to 36% in the experimental arm. Before pembrolizumab, stereotactic body radiotherapy was well tolerated. Although a doubling of ORR was noted, for meaningful clinical benefit, the results did not meet the preset endpoint criteria of the study. The programmed death–ligand 1–negative subgroup, which significantly improved progression-free survival and overall survival, greatly influenced positive results. These findings indicate that a larger trial is needed to determine whether non-inflamed NSCLC can be activated by radiotherapy towards a more inflamed tumor microenvironment.