Phase II trial of consolidative stereotactic body radiation therapy in patients with metastatic oncogene-driven non-small cell lung carcinoma treated with tyrosine kinase inhibitors

: 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 inhibitor (TKI) occur in originally involved sites and may lead to subsequent distant failures (DF). We sought to determine whether consolidative SBRT to residual sites reduces DF. : This is a single-arm, phase II 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. : Median follow-up was 57.1 months. The trial enrolled 27 of 30 planned patients between 2015 - 2021, stopping early due to slow accrual. Most (n = 22) had EGFR driver mutations. The majority (59.5%) were treated with later-generation TKIs. 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 PFS from SBRT was 15.0 months (95% CI, 8.6-46.7). Two-year LF rate of irradiated sites was 11% (95% CI, 3-27%). Two-year and median OS 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. : 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.