Durvalumab With Radiation Therapy in Patients With Inoperable Locally Advanced Non–Small Cell Lung Cancer Ineligible for Concurrent Chemoradiotherapy (DART)

PURPOSE Concurrent platinum-based chemotherapy and radiation therapy (cCRT) followed by consolidative durvalumab is the standard of care (SoC) for fit patients with inoperable, locally advanced non–small cell lung cancer (LA-NSCLC). However, no SoC exists for patients who are cCRT-ineligible because of age, comorbidities, or frailty. Here, we investigated the efficacy and adverse events (AEs) of concurrent and consolidative durvalumab with definitive radiation therapy (RT) without chemotherapy. METHODS In this multicenter, single-arm, prospective phase II study, patients received conventionally fractionated RT plus concurrent and consolidative durvalumab (1,500 mg fixed dose once every 4 weeks) for up to 12 months. The primary end point was 2-year progression-free survival (PFS) of 36% compared with historical results of 20% with sequential CRT (86% power). Additional end points included overall survival (OS) and cancer-specific survival (CSS). RESULTS Fifty-eight patients (median age 82 years [IQR, 76-86]; 16 [28%] PD-L1–negative; eight [14%] Eastern Cooperative Oncology Group [ECOG] score 2; 46 [79%] ECOG score 1; four [7%] ECOG score 0) were treated per protocol. The study met its primary end point with a 2-year PFS of 39% (one-sided CI, 29 to 100) and a 2-year OS of 54%. Better performance status and PD-L1 positivity were associated with improved PFS; better ECOG was associated with improved OS; PD-L1 positivity was associated with better CSS. Grade 3/4 treatment-related AEs occurred in 12 (21%) patients. Grade 5 AEs occurred in four (7%) patients (radiation pneumonitis (n = 2) and cardiac arrest (n = 2)). Durvalumab was discontinued early because of AEs in 18 (31%) patients. CONCLUSION Thoracic RT with concurrent and consolidative durvalumab is a promising treatment option for cCRT-ineligible patients with LA-NSCLC, demonstrating better PFS with a favorable safety profile compared with historical controls.