First-line tyrosine kinase inhibitor with or without aggressive upfront local radiation therapy in patients with EGFRm oligometastatic non-small cell lung cancer: Interim results of a randomized phase III, open-label clinical trial (SINDAS) (NCT02893332).
9508 Background: The effectiveness of aggressive local therapy for oligometastatic non-small-cell lung cancer (NSCLC) is unknown. This multi-institutional, randomized, open label, phase III clinical trial was performed to assess upfront stereotactic radiotherapy to all sites at diagnoses in previously untreated EGFRm oligometastatic non-small-cell lung cancer on progression-free survival and overall survival. Methods: The study was conducted at five centers located in different provinces of China.Eligible participants had pathologically confirmed adenocarcinoma, gene sequencing confirmed EGFRm, stage IV, five or fewer metastatic disease lesions, an ECOG performance status score of ≤ 2, systemic therapy naive, and no brain disease before randomization.Participants were randomized to receive either first-line tyrosine kinase inhibitor (TKI) treatment alone or up front stereotactic radiotherapy to all sites of disease along with TKI treatment.The primary endpoint was progression-free survival and the secondary endpoint was overall survival. Results: From January 2016 to January 2019, 133 participants were enrolled, including 65 (48.8%) in the TKI arm who received standard of care TKI alone and 68 (51.1%) in the stereotactic radiotherapy sites at diagnosis arm who received stereotactic radiotherapy and TKI.At a median follow-up of 19.6 months (IQR 9.4 - 41.0), the median progression-free survival for tyrosine kinase inhibitor alone was 12.5 months, and for tyrosine kinase inhibitor and stereotactic radiotherapy was 20.20months, respectively (HR 0.6188 [95% CI 0.3949-0.9697], log rank P< .001). The median overall survival in the TKI alone arm was 17.40 months, and for TKI and stereotactic radiotherapy arm was 25.50 months, respectively (HR 0.6824 [95% CI 0. 4654-1.001], log rank P< .001). Adverse events were similar between groups, with no grade 5 or deaths due to treatment. Grade 3/4 adverse events with or without radiotherapy included pneumonitis (7.3% vs. 2.9%; P> .05) and esophagitis (4.4%vs. 3.0% P> .05). Conclusions: Upfront stereotactic radiotherapy to sites at diagnosis along with first line TKI improved both progression-free survival and overall survival significantly compared with TKI alone. This finding suggests aggressive local therapy to sites at diagnosis should be explored further in large cohort phase III trials as a standard treatment option in this clinical scenario. Clinical trial information: NCT02893332 .