Radiation plus durvalumab without chemotherapy cleared its survival target in frail LA-NSCLC patients

No standard treatment exists for locally advanced NSCLC patients too frail for chemoradiotherapy

Concurrent platinum-based chemotherapy and radiation therapy, followed by consolidative durvalumab, is the standard of care for fit patients with inoperable, locally advanced non-small cell lung cancer. No standard of care exists for patients who cannot tolerate that regimen because of age, comorbidities, or frailty. The DART trial investigated whether concurrent and consolidative durvalumab given with definitive radiation therapy alone, without chemotherapy, could offer these patients an effective option.

A 58-patient, single-arm phase II trial of radiation and durvalumab without chemotherapy

DART was a multicenter, single-arm, prospective phase II trial. Patients received conventionally fractionated radiation therapy plus concurrent and consolidative durvalumab at a fixed dose of 1,500 mg every 4 weeks, for up to 12 months. The primary endpoint was set at a 2-year progression-free survival rate of 36%, against a historical benchmark of 20% with sequential chemoradiotherapy, powered at 86%.

Fifty-eight patients were treated per protocol. The median age was 82 (interquartile range, 76 to 86). Twenty-eight percent of patients were PD-L1-negative. By performance status, 7% had an ECOG score of 0, 79% had a score of 1, and 14% had a score of 2, a population skewed toward the older, lower-performance-status patients the trial was designed to serve.

The trial cleared its benchmark: 39% two-year progression-free survival against a 20% historical rate

The study met its primary endpoint. Two-year progression-free survival was 39% (one-sided confidence interval, 29 to 100), above both the 36% target and the 20% historical rate with sequential chemoradiotherapy. Two-year overall survival was 54%. Better performance status and PD-L1 positivity were associated with improved progression-free survival; better ECOG score was associated with improved overall survival; and PD-L1 positivity was associated with better cancer-specific survival.

The trial reports these results against a historical comparator rather than a randomized control arm, since it enrolled a single group of patients rather than randomizing between durvalumab-plus-radiation and an alternative regimen.

Grade 5 adverse events occurred in 7% of patients, including two cardiac arrests

Grade 3/4 treatment-related adverse events occurred in 12 patients (21%). Grade 5 adverse events, the most severe grade, occurred in 4 patients (7%): two cases of radiation pneumonitis and two cardiac arrests. Durvalumab was discontinued early because of adverse events in 18 patients (31%), just under a third of the cohort, in a population whose median age was 82.

“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.”Journal of Clinical Oncology (2026)

A single-arm result measured against history, not a randomized comparator

DART’s primary endpoint was met against a historical benchmark rather than a concurrently randomized control group, and the trial enrolled 58 patients at a single treatment stage rather than following a larger cohort past 2 years. The paper does not report median progression-free or overall survival in months, an objective response rate, or outcomes beyond the 2-year mark, so how the benefit holds up over a longer follow-up, and how it would compare in a randomized trial against a different chemotherapy-free regimen, are not established by this study.