Anti-PD-1 With or Without Radiotherapy for Oligometastatic Non-Small Cell Lung Cancer

PURPOSE/OBJECTIVE(S) Growing numbers of clinical trials with the aim of testing the efficacy of radiotherapy (RT) in combination with immunotherapy using single-site irradiation does not substantially increase the response rate in unselected metastatic patients. Oligometastatic disease with smaller disease burdens and low tumor heterogeneity suggested that radiotherapy to a single lesion with immunotherapy might be optimal. We hereby conducted a study to evaluate the effect of this combination on patients with oligometastatic non-small cell lung cancer (NSCLC). MATERIALS/METHODS We retrospectively identified oligometastatic NSCLC (≤4 metastatic sites) treated PD-1 pathway inhibitors with or without radiotherapy to a single lesion at our institution between 2018 and 2020. The 2 primary end points were best objective response rate (ORR) and progression-free survival (PFS) from the start of anti-PD-1 treatment. PFS was assessed using Kaplan-Meier estimates survival curves and Cox proportional hazards models were used for univariate analysis. RESULTS Of the 152 patients enrolled, 93 of whom had been identified as control arm (anti-PD-1 without RT) and 59 who had been identified as experimental arm (anti-PD-1 plus RT). The median follow-up time was 8.1 months. The best ORR was 41.3% in the experimental arm vs 31.2% in the control arm. The experimental arm had a median PFS of 13.8 months (95% CI, 9.5-18.1 months), significantly greater than the control arm with a median of 8.9 months (95% CI, 4.7-13.1 months) (HR, 0.568; P = 0.035). In subgroup analyses, a significant benefit of RT with respect to PFS was seen in patients aged < 65 years (P = 0.016), ECOG 0 patients (P = 0.048), patients with synchronous metastases (P = 0.012), patients with 1-2 metastatic foci (P = 0.024), and patients who received no previous chemotherapy (P = 0.009). One patient died due to immune-related pneumonitis; No unexpected adverse events or significantly increased toxicities were observed in the experimental arm. CONCLUSION Irradiating only a single lesion with anti-PD-1 inhibitors significantly increased systemic responses and survival outcomes in patients with oligometastatic NSCLC.