Phase 2 Trial of Consolidative Stereotactic Body Radiation Therapy in Patients With Metastatic Oncogene-driven Non-small Cell Lung Carcinoma Treated With Tyrosine Kinase Inhibitors.

Purpose: The role of stereotactic body radiation therapy (SBRT) in the management of advanced EGFR/ALK/ROS1-driven non-small cell lung carcinoma (NSCLC) remains undefined. In EGFR-mutant NSCLC, 50-60% of recurrences on first-line tyrosine kinase inhibitors (TKIs) occur in originally involved sites and may lead to subsequent distant failures (DFs). We sought to determine whether consolidative SBRT to residual sites reduces DF.

Methods And Materials: This is a single-arm, phase 2 trial of SBRT to residual sites of disease in patients with metastatic oncogene-driven NSCLC with stable or responding disease to TKI within 12 months of treatment start. The primary endpoint was DF frequency at 12 months after SBRT.

Results: The median follow-up was 57.1 months. The trial enrolled 27 of 30 planned patients between 2015 and 2021, stopping early caused by slow accrual. Most (n = 22) had EGFR driver mutations. The majority (59.5%) were treated with later-generation TKIs. The median time from TKI start to SBRT was 6.4 months. Twenty-five patients (92.6%) received SBRT to the residual lung primary only. The 12-month DF rate was 19% (95% CI, 7%-36%). Median progression-free survival from SBRT was 15.0 months (95% CI, 8.6-46.7). The 2-year local failure rate of irradiated sites was 11% (95% CI, 3%-27%). Two-year and median overall survival were 88% (95% CI, 68%-96%) and 59.6 months (95% CI, 42.3-NR), respectively. There were no grade ≥3 adverse events related to SBRT.

Conclusions: In patients treated with first-line TKIs, consolidative SBRT was associated with improvement in distant disease control compared with historical controls, supporting ongoing randomized trials.