Predictors of benefit to radiation for oligoprogressive disease in EGFR-mutant metastatic non-small cell lung cancer patients treated with osimertinib.

e21127 Background: While osimertinib has transformed the treatment paradigm of EGFR-mutant lung cancers (EGFR+ LC), all patients inevitably progress. Oligoprogression is a common pattern of progression for which radiation therapy (RT) can be utilized to prolong the time on osimertinib. However, data supporting the benefit of osimertinib in prolonging progression is limited. Furthermore, predictors of response to RT in the setting of oligoprogression are unknown. We aim to identify clinical and genomic factors associated with robust progression-free survival (PFS) after RT for oligoprogression in EGFR+ LC in patients treated with osimertinib. Methods: Patients with metastatic EGFR+ LC on osimertinib who underwent radiation from 2010 to 2022 for oligoprogression (i.e. progression in 5 or less lesions) were identified. Patients received RT to all active sites of intra- and extra- thoracic disease. Patients who progressed within 3 months of radiation therapy were classified as “rapid progressors,” and those that had longer PFS were “late progressors.” All cases underwent clinical and genomic annotation. Comparisons of categorical variables were performed by Fisher’s exact test. Results: 84 patients were identified who underwent RT for oligoprogression on osimertinib, of which 25% (n = 21) were rapid progressors. Median time from radiation to subsequent progression was 6 months (range 1-26mo) and upon progression most patients had growth of more than one lesion (71%). Median time to death or last follow-up was 13.5 months (range 1-48mo). There was no significant difference in gender, ethnicity, and baseline KPS between rapid and late progressors. Patients with baseline exon 19 deletion (63% vs 76%, p = 0.3) and atypical mutations (14% vs 3%, p = 0.1) were more likely to be rapid progressors while those with exon 21 L858R (10% vs 33%, p = 0.03) were more likely to be late progressors. Among the rapid progressors, 50% underwent radiation to the lung, 10% to the brain, 35% to the bone, and 5% to lymph nodes. Median size of the largest lesion and number of lesions was similar between the two groups (rapid 2.5 cm and 1.5 lesions vs late 2.7 cm and 1 lesion). In-field recurrence rate was 18% and did not differ between rapid and late progressors (14% vs 19%). Conclusions: Radiation therapy for oligoprogression results in clinically meaningful time on osimertinib beyond progression for many patients. However, 25% of patients rapidly progress after radiation therapy and should be directed to switch systemic therapy. Further study is needed to better elucidate benefit at the time of radiation, so that the systemic treatment approach for these patients can be optimized.