Osimertinib dose-reduction and survival in 1L EGFR-mutated metastatic non-small cell lung cancer (mNSCLC)

INTRODUCTION: Osimertinib has become standard of carein 1 LEGFR-mutated(mt)mNSCLC following the FLAURA trial.However, limited data are available on the effect of osimertinib dose-reductionon outcomes compared tofull-dose. METHODS: We performed a single-institution, retrospective analysis of pts withEGFR-mt mNSCLC treated with 1 L osimertinib from 2018 to 2023. Pts who underwent dose-reduction were compared to thosemaintained on full dose (80 mg daily). Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record and compared using independent sample t-tests and chi-square analyses as appropriate. Median progression free survival (mPFS), time to discontinuation (mTTD), and overall survival (mOS) were compared via Kaplan-Meier log-rank test and Cox regression analysis with time-varying covariate. RESULTS: Of 171 pts with mNSCLC treated with 1 L osimertinib, 26 (15%) required dose-reduction. Sex (p = 0.458), race (p = 0.421), ECOG PS > 1 at diagnosis (p = 0.730) and smoking history (p = 0.485) were comparable between reduced-dose and full-dose pts. 44% vs 34% of reduced dose and full dose pts, respectively, had CNS metastases at diagnosis (p = 0.192). All dose-reduced pts experienced adverse events (AEs), compared to 48% of full-dose pts (p < 0.001). Dose-reduced pts had shorter mPFS compared to full-dose pts (17.0 vs 24.6 mos; p = 0.043). Median PFS with dose-reduction was shorter compared to full-dose in pts with (p = 0.041) or without CNS metastases (p = 0.048). On time-variate, multivariable analysis, dose-reduction was associated with inferior PFS (p = 0.047) regardless of baseline characteristics. TTD was comparable in pts with and without dose-reduction (21.3 vs 25.2 mos; p = 0.521) OS was comparable in pts with and without dose-reduction (36.7vs 39.2 mos; p = 0.749). 14 pts (8%) discontinued osimertinib 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). CONCLUSION: Dose-reduction of osimertinib was relatively uncommon and associated with shorter PFS (primarilyCNS progression), but similar TTD and OS in 1 L patients withEGFR-mutated mNSCLC.