Efficacy and pattern failures of early SBRT to primary tumor in advanced EGFR mutation lung cancer (Target-SBRT): A single-arm phase 2 study.

e21130 Background: It is evitable for advanced NSCLC harboring EGFR mutation with 1st TKI to develop resistance with 9-13 months of PFS and 19-27 months of OS. Initial progression of TKI treatment in NSCLC was 47.2% from the primary sites, 20.4% from the new sites and 32.6% from the primary and new sites. We hypothesized that early stereotactic body radiation therapy (SBRT) to primary tumor in advanced EGFR mutation NSCLC combined with EFGR-TKI treatment could prolong targeted resistance and explored its pattern failures. Methods: Eligible patients pathologically confirmed advanced NSCLC with Exon19 deletion or Exon21 L858R mutation were enrolled (ChiCTR-OIN-17013920). Each patient received EGFR TKI (Icotinib 125mg tid or gefitinib 250mg qd) and early SBRT (40-60 Gy/5-8F/5-10d) for primary tumor about 1 months from the beginning of EGFR TKI until disease progressed. Initial progression in sites of original disease (primary/metastatic) was defined as original site failure (OF) and appearance of new lesions as distant site failure (DF). Simultaneous OF/DF was labeled as ODF. The primary endpoint was PFS and the second endpoints were pattern failures, OS as well as adverse effects (AEs). Study was designed to enroll 50 patients to detect 6 months’ extension of PFS. Results: The study was closed after 41 patients enrolled due to the use of more effective 3rd EGFR-TKI.There were 37 PR and 4 SD after one month of TKI treatment and the average tumor shrinkage rate was 42.5%. The average interval from TKI to SBRT was 1.43 months (0.87-2.77 months). Median PFS and OS were 15.2 months (95% CI 13.1-17.4) and 27.6 months (95% CI 23.1-32.1), respectively. Of 37 patients who progressed, 6 (16.2%) had OF, 21 (56.8%) had DF, and 10 (27.0%) had ODF. The lung was the most common site of initial progression. As for toxicity, there was no ≥Grade 3 AEs and Grade 1-2 radiation Pneumonitis was the most frequent AEs. Conclusions: Early SBRT for primary tumor generated prolonged PFS without serious radiation pneumonitis in advanced EGFR mutation NSCLC patients with TKI treatment. This combined therapy obtained remarkably lower primary tumor progression rate and favorable OS. Clinical trial information: ChiCTR-OIN-17013920.