In a phase II trial reported in The Lancet Oncology, Heinzerling et al found that primary lung tumor stereotactic body radiotherapy (SBRT) followed by concurrent mediastinal chemoradiotherapy (with or without adjuvant immunotherapy) was associated with activity in patients with locally advanced non–small cell lung cancer (NSCLC).
Study Details
In the U.S. multicenter trial, 61 patients were enrolled between May 2017 and June 2022 from 8 regional centers in North Carolina and South Carolina. Patients received SBRT to the primary tumor (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 with concurrent platinum-doublet chemotherapy (either 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 on days 1, 8, 29, and 36 for two cycles of 4 weeks). Protocol amendments allowed consolidation durvalumab at the discretion of the treating investigator and, subsequently, directed patients without disease progression after chemoradiotherapy to receive consolidation durvalumab (10 mg/kg on days 1 and 15 of a 4-week cycle for up to 12 cycles or 1,500 mg on day 1 of a 4-week cycle for up to 12 cycles). The primary endpoint was 1-year progression-free survival.
Key Findings
Of 61 patients, 47 received at least one dose of consolidation durvalumab. Among 59 evaluable patients, 46 received durvalumab. Median follow-up was 29.5 months.
Among the 59 evaluable patients, the 1-year progression-free survival rate was 62.7% (90% confidence interval [CI] = 51.2%–73.2%, one-sided P = .39 vs historical control rate). Among the patients who received durvalumab, the 1-year progression-free survival rate was 69.6% (90% CI = 56.6%–80.6%, one-sided P = .12 vs historical control rate).
Among all 61 patients, the most common grade 3 or 4 treatment-related adverse events were decreased neutrophil count (15%), decreased white blood cell count (8%), and anemia (7%). Treatment-related serious adverse events occurred in 18%, most commonly lung infection (5%). Treatment-related death was reported in four patients (7%), because of 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 tumour SBRT followed by concurrent mediastinal chemoradiotherapy were favourable compared with other modern trials treating locally advanced NSCLC with chemoradiotherapy. These findings serve as the basis for the ongoing randomised phase 3 study NRG Oncology LU008 (NCT05624996).”
John H. Heinzerling, MD, of the Department of Radiation Oncology, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by AstraZeneca and Atrium Health Levine Cancer Institute. For full disclosures of the study authors, visit thelancet.com.
