Interim results of a phase II study have demonstrated the safety and feasibility of treating elderly and frail patients with locally advanced non–small cell lung cancer (NSCLC) with the monoclonal antibody durvalumab during and after radiation therapy, without chemotherapy. The results of a preplanned interim analysis of the DART trial were presented at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer.1
“No early stopping safety rule was met. One patient experienced grade 5 pneumonitis. Preliminary progression-free survival and overall survival appear superior to historical results of sequential chemoradiotherapy or radiotherapy alone [ie, without durvalumab],” said the study’s principal investigator Andreas Rimner, MD, Director of Thoracic Radiation Oncology Research and Associate Attending at Memorial Sloan Kettering Cancer Center, New York.
Andreas Rimner, MD
“The current standard of care for newly diagnosed inoperable locally advanced non–small cell lung cancer is concurrent chemoradiation therapy followed by consolidative durvalumab. However, up to 50% of patients are not candidates for this approach and thus are treated with sequential chemoradiotherapy or radiation therapy alone—a setting in which immunotherapy is not approved,” Dr. Rimner said. “We launched an investigator-initiated trial to study the safety and outcomes of concurrent and consolidative durvalumab and radiation therapy without chemotherapy in patients who are not candidates for concurrent chemoradiotherapy,” he explained.
The single-arm open-label phase II study evaluated concurrent and consolidative durvalumab and radiation therapy without chemotherapy in an elderly and frail population of 27 patients with locally advanced NSCLC, unselected for expression of PD-L1. The current analysis was preplanned based on 50% enrollment (n = 27). Most patients had adenocarcinoma, disease stage IIIA, and an Eastern Cooperative Oncology Group performance status of 1.
Patients were treated with definitive conventionally fractionated radiotherapy (54–66 Gy in 27–33 fractions) along with durvalumab at 1,500 mg every 4 weeks, initiated within 7 days of starting radiotherapy; durvalumab at 1,500 every 4 weeks was continued for up to 13 cycles. Patients did not receive chemotherapy.
At the time of the interim analysis, the median follow-up of the first 27 patients was 12 months (range, 3.3–27.7 months). For the 21 patients for whom PD-L1 status was available, 11 had PD-L1 expression of more than 1%, and 5 patients had PD-L1 expression of more than 50%. In the 16 patients for whom tumor mutation burden was assessed, the median was 10.5 mutations/megabase.
At 1 year, progression-free survival was 41.8%, and median progression-free survival was 10.1 months. Overall survival rates were 74.8% at 1 year and 55.4% at 18 months; median overall survival was 20.3 months, Dr. Rimner reported. The researchers pointed out, in their poster, that previously reported 1-year overall survival with radiotherapy alone or with sequential chemoradiotherapy had been 40% to 60%.2-4 Three treatment-related serious adverse events were observed in the first 27 patients.
DISCLOSURE: The study is an investigator-initiated study with funding and drug supply by AstraZeneca. Dr. Rimner has received grants and/or consulting fees from Varian Medical Systems, AstraZeneca, Merck, Pfizer, Boehringer Ingelheim, and MoreHealth.
1. Rimner A, Fitzgerald K, Iqbal AN, et al: Planned interim analysis of a phase II trial of concurrent durvalumab and radiation therapy for locally advanced lung cancer. 2022 World Conference on Lung Cancer. Abstract EP05.01-025. Presented August 7, 2022.
2. Dillman RO, Herndon J, Seagren SL, et al: Improved survival in stage III non-small-cell lung cancer. J Natl Cancer Inst 88:1210-1215, 1996.
3. Sonnick MA, Oro F, Yan B, et al: Identifying the optimal radiation dose in locally advanced non-small-cell lung cancer treated with definitive radiotherapy without concurrent chemotherapy. Clin Lung Cancer 19:e131-e140, 2018.
4. Sause W, Kolesar P, Taylor IS, et al: Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer. Chest 117:358-364, 2000.