Factors Associated with Outcomes in Patients with Metastatic NSCLC Receiving Osimertinib and Consolidative Radiation Therapy

Abstract

<h3>Purpose/Objective(s)</h3> Outcomes for EGFR-mutated non-small cell lung cancer (NSCLC) have improved significantly with the development of osimertinib (osi), a 3^rd generation EGFR tyrosine kinase inhibitor (TKI). Effective management of oligoprogressive and oligopersistent disease on osi has become more clinically relevant, however current data is sparse. We aim to identify factors associated with improved outcomes for consolidative RT to guide clinicians prior to the completion of ongoing randomized studies. <h3>Materials/Methods</h3> We conducted a single-institution retrospective study of patients with histologically confirmed, metastatic NSCLC treated with osi and consolidative RT from 2015-2021. Consolidative RT was defined as EGFR TKI. Oligoprogression was defined as size increase of ≤5 lesions, while oligopersistent disease was defined by stable or decreased lesion size after EGFR TKI. Univariable analysis (UVA) was performed using the Cox proportional hazards model for progression-free survival (PFS) and overall survival (OS), measured from end of consolidative RT. <h3>Results</h3> Patient demographics are listed in 1. < 3 lesions at time of consolidative RT (HR 0.27; p=0.046) and EGFR T790M mutation (HR 0.27; p=0.015) was associated with improved PFS. EGFR L858R mutation was associated with shorter PFS (HR 3.06, p=0.025) and size of largest treated lesion approached significance for shorter PFS (HR 1.47; p=0.056). Tumor size by TNM staging (HR 1.5; p=0.053) and EGFR T790 mutation (HR 0.27; p=0.058) approached significance for OS. <h3>Conclusion</h3> In the setting of consolidative RT after osi, improved PFS correlated with < 3 lesions at the time of consolidative RT and EGFR T790 mutation. PFS decrease was correlated with largest treated lesion size and EGFR L858R mutation. This suggests that radiation for oligoprogressive or oligopersistent disease may offer clinical benefit to selected patients, particularly those with less than 3 sites of active disease or limited lesion size. Further investigation in a prospective setting is warranted.