Management of oligoprogressive EGFR+ NSCLC in the age of osimertinib: A single center experience.

e20656 Background: Oligoprogressive disease (OPD), often defined as <5 progressing lesions, is common in patients with EGFR+ NSCLC who progress while receiving osimertinib. Consideration of local therapy (LT; radiation or surgical resection) is recommended by National Comprehensive Cancer Network (NCCN) guidelines in the setting of OPD with continued targeted therapy. However, the degree to which LT is used in OPD in current practice is not well described. We aimed to evaluate and describe management strategies for OPD in osimertinib treated EGFR+ NSCLC at an NCI-designated cancer center. Methods: Retrospective EMR review of 161 patients with metastatic EGFR+ NSCLC treated at Northwestern Memorial Hospital between 1/1/2016 and 1/1/2025 included assessment of progression pattern (OPD if <5 lesions), tumor genomics, and therapy prior to/following progression. Fisher’s exact test was used to determine strength of associations between assessed variables and therapeutic strategy. Results: 60 (37.2%) patients with OPD who were on osimertinib at time of progression were identified. Most patients had a change in systemic therapy (ST) without LT (53.4%) at progression; of those patients, 58.1% transitioned to a non-osimertinib regimen. 13.8% of patients with OPD had a change in ST in addition to LT. For the 24.1% receiving LT without ST change (50% stereotactic body radiotherapy, 43% stereotactic radiosurgery of the CNS, 7% surgical resection), mean time to change in ST after LT was 10.3 months (95% CI 5.0-15.6). Those with time to progression on osimertinib ≥24 months were significantly more likely to receive LT without change in ST (41.6% vs 19.6%, p=0.02); , age, number of sites, and tumor genomics including EGFR mutation did not significantly impact therapeutic strategy. Conclusions: LT in OPD in EGFR+ NSCLC has been associated with improved outcomes, but current implementation may be limited. Our single center analysis demonstrated most patients did not receive LT despite OPD, regardless of age, number of sites, or mutational profile, although patients with longer time to progression on osimertinib were more likely to receive LT. While our study is limited as a single center analysis, our results suggest further study is needed for evidence based guidelines development for LT implementation in OPD. Patient and disease specific factors and their association with therapeutic strategy in EGFR+ NSCLC OPD. Change in ST alone (N=31) Change in ST, with LT (N=8) LT, without change in ST (N=14) No change in therapy (N=5) p value Age <65 17 (53%) 5 (16%) 8 (25%) 2 (6%) - Age ≥65 14 (56%) 3 (13%) 6 (25%) 3 (13%) 0.56 1-2 sites 17 (51%) 5 (15%) 8 (24%) 3 (9%) - 3-4 sites 14 (56%) 3 (12%) 6 (24%) 2 (8%) 1.0 <24 months to progression 29 (63%) 5 (6%) 3 (10%) 9 (20%) - ≥24 months to progression 2 (37%) 3 (25%) 2 (12%) 5 (25%) 0.02 New mutation(s) at progression 17 (52%) 3 (9%) 10 (30%) 3 (9%) - No new mutations identified 14 (56%) 5 (20%) 4 (16%) 2 (8%) 0.47