Benchmarking Outcomes for Molecularly Characterized Synchronous Oligometastatic Non-Small-Cell Lung Cancer Reveals <i>EGFR</i> Mutations to Be Associated With Longer Overall Survival.

Abstract

Local consolidative therapy (LCT) for patients with synchronous oligometastatic non-small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients. We identified all patients presenting between 2000 and 2017 with stage IV non-small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis. Of 194 included patients, 121 received comprehensive LCT to all sites of disease with either surgery or radiation. <i>TP53</i> mutations were identified in 40 of 78 (55%), <i>KRAS</i> in 32 of 95 (34%), <i>EGFR</i> in 24 of 109 (22%), and <i>STK11</i> in nine of 77 (12%). At median follow-up of 96 months, median OS and PFS were 26 (95% CI, 23 to 31) months and 11 (95% CI, 9 to 13) months, respectively. On multivariable analysis, patients with <i>EGFR</i> mutations had lower mortality risk (hazard ratio [HR], 0.53; 95% CI, 0.29 to 0.98; <i>P</i> = .044) compared with wild-type patients, and patients with <i>STK11</i> mutations had higher risk of progression or mortality (HR, 2.32; 95% CI, 1.12 to 4.79; <i>P</i> = .023) compared with wild-type patients. <i>TP53</i> and <i>KRAS</i> mutations were not associated with OS or PFS. Among 71 patients with known <i>EGFR</i> mutational status who received comprehensive LCT, <i>EGFR</i> mutations were associated with lower mortality compared with wild-type (HR, 0.45; 95% CI, 0.22 to 0.94; <i>P</i> = .032). When compared with wild-type patients, those with <i>EGFR</i> and <i>STK11</i> mutations had longer OS and shorter PFS, respectively. <i>EGFR</i> mutations were associated with longer OS among oligometastatic patients treated with comprehensive LCT in addition to systemic therapy.