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.