In a phase II study published in the Journal of Clinical Oncology, Rimner et al found that concurrent and consolidative durvalumab administered with definitive radiation therapy, without chemotherapy, demonstrated encouraging efficacy in patients with inoperable locally advanced non–small cell lung cancer (NSCLC) who were ineligible for concurrent chemoradiotherapy.
Study Details
The DART study was a prospective, multicenter, single-arm phase II trial that enrolled patients with newly diagnosed or recurrent, surgically unresectable or medically inoperable locally advanced NSCLC who were considered unfit for platinum-based concurrent chemoradiotherapy because of advanced age, comorbidities, frailty, or poor performance status. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and no actionable driver mutations. Between August 2019 and July 2023, 58 patients initiated protocol therapy. The median age was 82 years (interquartile range = 76–86 years).
Patients received definitive thoracic radiotherapy (54–66 Gy) beginning within 7 days of treatment initiation together with durvalumab at a fixed dose of 1,500 mg every 4 weeks for up to 13 cycles. The primary endpoint was 2-year progression-free survival (PFS), with the investigators aiming to improve the historical 2-year PFS of 20% reported with sequential chemoradiotherapy to 36%.
Key Results
The study achieved its primary endpoint, with a 2-year PFS of 39% (one-sided confidence interval [CI] = 29%–100%) and a median PFS of 14 months (95% CI = 9.3 months to not reached). PFS rates were 78% (95% CI = 67%–90%) at 6 months, 55% (95% CI = 42%–71%) at 12 months, and 39% (95% CI = 27%–57%) at 24 months. Median overall survival (OS) was 25 months (95% CI = 17 months to not reached), with OS rates of 83% (95% CI = 73%–94%), 78% (95% CI = 67%–91%), and 54% (95% CI = 40%–73%) at 6, 12, and 24 months, respectively.
Among evaluable patients, the objective response rate was 72% and the disease control rate was 87%. Better ECOG performance status was significantly associated with improved PFS and OS, while PD-L1 positivity was associated with improved cancer-specific survival and longer median OS compared with PD-L1 negativity.
Grade 3 or 4 adverse events were reported in 21% of patients, and grade 5 adverse events occurred in 7%, including two deaths attributed to pneumonitis and two to cardiac arrest. Immune-related adverse events occurred in 86% of patients overall, and 18 patients (31%) discontinued durvalumab because of adverse events, most commonly pneumonitis or hypoxia.
The investigators concluded: “Thoracic [radiotherapy] with concurrent and consolidative durvalumab is a promising treatment option for [concurrent chemoradiotherapy]–ineligible patients with [locally advanced] NSCLC, demonstrating better PFS with a favorable safety profile compared with historical controls.”
Andreas Rimner, MD, of the Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by AstraZeneca and the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
