Outcomes After Radiation for Oligoprogressive Disease Sites in Patients With EGFR -Mutant Lung Cancer Treated With Osimertinib

PURPOSE Oligoprogressive disease (OPD) commonly occurs in patients with advanced EGFR mutation–positive non–small cell lung cancer (EGFR+ LC) on systemic therapy. While radiation therapy (XRT) to treat OPD can improve outcomes, the clinical and genomic predictors of benefit from local therapy for oligoprogression on osimertinib are unclear. METHODS We conducted a single-center retrospective analysis of 81 patients with EGFR+ LC on osimertinib who received XRT for OPD (defined as progression in ≤5 lesions) between January 2014 and December 2022. Progression patterns were identified. Times from local therapy to progression, next therapy, and death were measured. RESULTS The median duration of osimertinib treatment before XRT was 16.9 months. After XRT, time on osimertinib was extended for a median of 9.7 months, with a median progression-free survival (PFS) and overall survival of 6.9 and 24.4 months, respectively. Post-XRT recurrence was most common in the lung (43%), viscera (35%), and bone (35%), with only 15% of patients experiencing in-field recurrence. Patients receiving XRT to lymph nodes or visceral metastases exhibited shorter PFS compared with other sites. EGFR mutation type, concurrent TP53 / RB1 mutations, and mechanisms of resistance did not significantly predict outcomes. CONCLUSION The addition of XRT for OPD led to clinically meaningful time on continued osimertinib beyond progression, irrespective of molecular characteristics or resistance mechanisms.