A phase II trial has explored the efficacy of primary lung tumor stereotactic body radiotherapy (SBRT) followed by concurrent mediastinal chemoradiotherapy and consolidative immunotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). While the study did not meet its primary endpoint, the combination demonstrated promising activity and safety profiles, warranting further investigation.
The multicenter, single-arm trial, published in The Lancet Oncology, enrolled 61 patients with unresectable stage II-III NSCLC. Participants received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiotherapy (up to 60 Gy in 30 fractions) to the involved lymph nodes with concurrent platinum doublet chemotherapy. A protocol amendment allowed for consolidation durvalumab in patients without disease progression after chemoradiotherapy.
Key Findings
With a median follow-up of 29.5 months, the 1-year progression-free survival rate was 62.7% (90% CI 51.2-73.2%), which did not significantly exceed the historical control rate (p=0.39). However, among patients who received consolidation durvalumab, the 1-year progression-free survival rate was 69.6% (90% CI = 56.6%-80.6%, P = .12 vs the historical control rate.
The most common grade 3-4 treatment-related adverse events were decreased neutrophil count (15%), decreased white blood cell count (8%), and anemia (7%). Treatment-related deaths occurred in 7% of patients, due to respiratory failure, lung infection, or pneumonitis.
Comparison with Prior Trials
Notably, the authors pointed out that although the trial did not meet its primary endpoint, the 1-year PFS data were improved compared with other studies, particularly the phase 3 PACIFIC study (NCT02125461), with 69.6% vs the rate of 55.7% in the PACIFIC trial.
Ongoing Research
John H. Heinzerling, MD, of the Department of Radiation Oncology, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, the corresponding author of The Lancet Oncology article, and colleagues noted that the findings serve as the basis for the ongoing randomized phase 3 study NRG Oncology LU008 (NCT05624996).
"This single-arm phase 2 study, evaluating full-dose SBRT to the primary tumor followed by conventional chemoradiotherapy to the involved nodes and consolidation immunotherapy, showed promising activity and safety," the authors wrote in the study. "We eagerly anticipate the results of the randomized phase 3 trial comparing this regimen with standard chemoradiotherapy in locally advanced NSCLC."
