Survival after osimertinib dose-reduction, discontinuation in 1L <i>EGFR</i> -mutated metastatic non-small cell lung cancer (mNSCLC).

8587 Background: Osimertinib (osi) has become standard of care in 1L EGFR mt (+) mNSCLC following the FLAURA trial in patients (pts) with classical sensitizing mutations. However, limited data are available on the effect of osimertinib dose reductions on survival outcomes compared to pts on full dose. Methods: We performed a single-institution retrospective analysis of pts with EGFR -mutated mNSCLC treated with 1L osi from 2018-2023 Clinical trial pts were excluded. Pts who underwent dose reduction were compared to those maintained on full dose (at least 80mg daily). Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record (EMR) and compared using independent sample t-tests and chi-square analyses as appropriate. Median progression free survival (mPFS) and overall survival (mOS) were compared via Kaplan-Meier log-rank analysis and Cox regression analysis, with sex, race, age, PS, smoking hx, CNS involvement, and mutation status included a priori . Results: 171 pts with mNSCLC treated with 1L osi were identified. 26 (15%) required dose reduction. Patient sex (p=0.458), racial distribution (p=0.421), ECOG PS&gt;1 at diagnosis (p=0.730) and smoking history (p=0.485) were comparable between reduced dose and full dose pts (Table 1). 44% vs 34% had CNS metastases at diagnosis (p=0.192). Rates of TP53 (p=0.712) and atypical EGFR mutations (p=0.393) were also comparable. All dose-reduced pts experienced AEs, compared to 48% of full-dose pts (p&lt;0.001). Dose-reduced pts had inferior mPFS (17.0 months [11.5-22.5]) compared to full-dose pts (24.6[19.2-28.8]; p=0.043. PFS with dose-reduction was inferior compared to full dose with (p=0.041) or without CNS metastases (p=0.048). On multivariable analysis, dose-reduction was associated with inferior PFS (p=0.047) regardless of baseline characteristics. OS, however, was comparable in pts with and without dose-reduction (36.7 [28.1-45.4] vs 39.2 [34.8-43.7]; p=0.749)). 14 pts (8%) discontinued osi due to AEs, of whom 9 (64%) were previously dose reduced. mPFS was comparable (p=0.334) between pts who discontinued and those who did not, as was mOS (p=0.910). Conclusions: Dose reduction of osimertinib was relatively uncommon and associated with inferior PFS but similar OS in 1L pts with EGFR -mutated mNSCLC. Baseline characteristics and survival. Baseline Characteristics Dose reduced (n=26) Full dose (n=145) Sig (p) Female 59.6% 63.0% 0.458 Race 0.421 White 63.0% 67.0% Black 3.7% 12.3% Asian 33.3% 19.1% ECOG PS&gt;1 0% 6.8% 0.730 Smoking Hx 37.0% 39.7% 0.485 CNS mets 44.4% 33.5% 0.192 Mutation Status TP53 55.7% 53.1% 0.712 L858R 35.8% 38.2% 0.675 Exon19del 45.7% 45.0% 0.819 Atypical mutation 18.5% 16.8% 0.393 Adverse Events (AEs) Experienced AEs 100% 48.3% &lt;0.001 Discontinued due to AE 34.6% 3.4% &lt;0.001 Survival (months) mPFS 17.0[11.5-22.5] 24.6[19.2-28.8] 0.043 mOS 36.7 [28