Durvalumab Combined With Chemotherapy and SABR Therapy in Patients With Oligometastatic Non-small Cell Lung Cancer: A Multicenter Phase 2 Study.

Abstract

Immunotherapy plus chemotherapy is the standard of care for driver-gene negative metastatic non-small cell lung cancer (NSCLC). Synchronous oligometastatic disease has a better prognosis than extensive metastasis, and the addition of stereotactic ablation body radiotherapy (SABR) results in improved efficacy. However, whether the combination of SABR with immunotherapy and platinum-doublet chemotherapy will lead to long-term disease control or even cure for patients remains unclear. This was a multicenter, phase 2, single-arm study to evaluate the efficacy and safety of durvalumab in combination with chemotherapy and SABR for oligometastatic stage IV NSCLC without previous systemic therapy. The primary endpoint was investigator-assessed progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors version 1.1. Thirty-five patients were enrolled in the study. Twenty-eight (80%) patients received radiation therapy, including 23 (65.7%) who received SABR. The median follow-up time was 24.7 months (95% CI, 21.6-27.5). In the full analysis set (n = 35), the median PFS (mPFS) was 10.4 months (95% CI, 4.4-26.1), and the 2-year PFS rate and overall survival (OS) rate were 38.5% (95% CI, 21.9-54.8) and 67.7% (95% CI, 49.0-80.7), respectively. In the per-protocol set (n = 32), mPFS was 14.6 months (95% CI, 4.7-26.1), and the 2-year PFS rate and OS rate were 42.4% (95% CI, 24.3-59.4) and 70.8% (95% CI, 51.2-83.8), respectively. The subgroup analysis showed that the mPFS was 24.3 months (95% CI, 7.6-NE) with SABR versus 3.1 months (95% CI, 1.4-4.7) without SABR (hazard ratio [HR], 0.2; 95% CI, 0.09-0.5; P < .001). Grade 3 or higher treatment-related adverse events (TRAEs) and immune-mediated adverse events (imAEs) were reported in 57.1% (20/35) and 25.7% (9/35) of patients, respectively. In oligometastatic NSCLC, the combination of durvalumab, chemotherapy, and SABR was effective and tolerable. Patients who did not experience disease progression after prior systemic therapy and received SABR might have optimal outcomes.