Phase 2 trial of durvalumab with radiation therapy for inoperable LA-NSCLC in patients ineligible for concurrent chemoradiotherapy

Concurrent platinum-based chemotherapy and radiation therapy (cCRT) followed by consolidative durvalumab is the standard of care for fit patients with inoperable, locally advanced non-small cell lung cancer (LA-NSCLC). The multicenter phase 2 DART trial evaluated conventionally fractionated RT plus concurrent and consolidative durvalumab (1500 mg every four weeks for up to 12 months) for patient ineligible for cCRT because of age, comorbidities, or frailty. The primary endpoint was 2-year progression-free survival rate of 36% compared with historical results of 20% with sequential CRT. Fifty-eight patients (median age 82 years; IQR 76-86; 28% PD-L1-negative; 14% ECOG score 2; 79% ECOG score 1; 7% ECOG score 0) were treated. The 2-year PFS was 39% (one-sided CI 29-100), meeting the primary endpoint. The 2-year overall survival (OS) rate was 54%. Better performance status and PD-L1 positivity were associated with improved PFS, better ECOG status was associated with improved OS, and PD-L1 positivity was associated with better cancer-specific survival. Grade 3-4 treatment-related adverse events occurred in 21%; grade 5 AEs occurred in 7%; early discontinuation of durvalumab because of AEs was reported for 31%. The authors conclude that thoracic RT with concurrent and consolidative durvalumab is a promising treatment option for cCRT-ineligible patients with LA-NSCLC.