In a phase II trial reported in The Lancet Oncology, Heinzerling et al found evidence of efficacy of primary lung tumor stereotactic body radiotherapy (SBRT) followed by concurrent mediastinal chemotherapy and consolidative immunotherapy in patients with locally advanced non–small cell lung cancer (NSCLC) with no prior radiotherapy or systemic therapy.
Study Details
In the trial, 61 patients from sites in North Carolina and South Carolina, enrolled between May 2017 and June 2022, were treated with: SBRT to the primary tumor at 50–54 Gy in 3–5 fractions, followed by standard radiotherapy planned up to 60 Gy in 30 2-Gy fractions to the involved lymph nodes and concurrent platinum doublet chemotherapy (paclitaxel at 50 mg/m² plus carboplatin AUC = 2 every 7 days for a total of six 1-week cycles or etoposide at 50 mg/m² on days 1–5 and days 29–33 plus cisplatin at 50 mg/m² intravenously on days 1, 8, 29, and 36 for two 4-week cycles. A protocol amendment allowed patients without disease progression after chemoradiotherapy to receive consolidation durvalumab at 10 mg/kg on days 1 and 5 of a 4-week cycle for up to 12 cycles or 1,500 mg day 1 of a 4-week cycle for up to 12 cycles. The primary endpoint was 1-year progression-free survival.
Key Findings
Median follow-up was 29.5 months (interquartile range = 14.9–47.1 months). A total of 47 patients received at least one dose of consolidation durvalumab.
Among the total of 59 eligible patients evaluated for the primary endpoint, progression-free survival at 1 year was 62.7% (90% confidence interval [CI] = 51.2%–73.2%), which did not significantly exceed the historical control rate (P = .39). Among patients who received durvalumab, 1-year progression-free survival was 69.6% (90% CI = 56.6%–80.6%, P = .12 vs the historical control rate.
Among 61 patients who received study treatment, median progression-free survival was 25.3 months, and 12- and 24-month rates were 62.8% and 51.1%. Median overall survival was 47.1 months, with 12- and 24-month rates of 80.3% and 60.0%.
The most common grade 3/4 treatment-related adverse events were decreased neutrophils (15%) decreased WBCs (8%), and anemia (7%). Treatment-related serious adverse events occurred in 18%, including lung infection (5%), pneumonitis (3%), decreased neutrophils (3%), and febrile neutropenia (3%). Treatment-related death occurred in four patients (7%), due to respiratory failure, respiratory failure and dyspnea, lung infection, and pneumonitis.
The investigators concluded: “Although this study did not meet the primary endpoint, activity, and safety profiles of primary lung [tumor] SBRT followed by concurrent mediastinal chemoradiotherapy were [favorable] compared with other modern trials treating locally advanced NSCLC with chemoradiotherapy. These findings serve as the basis for the ongoing [randomized] phase III study NRG Oncology LU008 (NCT05624996).”
John H. Heinzerling, MD, Department of Radiation Oncology, Levine Cancer Institute, Atrium Health, Charlotte, NC, is the corresponding author for The Lancet Oncology article.
Disclosures: The study was funded by AstraZeneca and Atrium Health Levine Cancer Institute. For full disclosures of all study authors, visit The Lancet.
