Efficacy and safety analysis of furmonertinib in the treatment of EGFR -mutated lung adenocarcinoma: A single-center real-world study based on high-risk stratification.

8651 Background: Real-world data on furmonertinib, a third-generation EGFR-TKI, for high-risk EGFR-mutant NSCLC patients (e.g., with brain metastasis, high tumor burden) are limited. This study evaluated its efficacy and safety via risk stratification. Methods: This retrospective study included 98 patients with locally advanced/metastatic EGFR-mutant NSCLC treated with furmonertinib (first-or later-line) from Sep 2021 to Dec 2024. Patients were stratified into high-risk (n = 73) and non-high-risk (n = 25) groups based on predefined criteria (brain/leptomeningeal metastases, high tumor burden, key co-mutations like TP53, or acquired T790M). Primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, DCR, iORR, iPFS, and OS. Safety assessed TRAEs (CTCAE v5.0). Results: Median follow-up was 17.7 months. In first-line group (n = 43), ORR was 69.8%, DCR 83.72%; in later-line group (n = 55), ORR was 64%, DCR 72.73%. PFS did not differ significantly between lines (P = 0.22). Median PFS was not reached overall. High-risk stratification analysis showed median PFS of 26.41 months in non-high-risk group vs not reached in high-risk group, with significant difference (P = 0.009). However, PFS rates showed a time-dependent effect: non-high-risk group had higher early PFS (96.0% vs 76.0% at 6 months), but high-risk group showed higher late PFS (98.6% vs 52.9% at 24 months). A time-dependent model confirmed high-risk features were detrimental early (HR = 33.03, P = 0.016) but protective after 6 months (interaction HR = 0.01, P = 0.001). In patients with measurable brain metastases (n = 39), iORR was 79.5%; median iPFS was not reached. TP53 co-mutation within high-risk group did not affect PFS (P = 0.731). TRAEs occurred in 15.3% (all grade 1-2, most common rash 5.1% and diarrhea 4.1%). Grade ≥3 events occurred in 6.1%, primarily elevated transaminases. No dose adjustments/discontinuations or fatal toxicities occurred. Conclusions: Furmonertinib showed durable efficacy in EGFR-mutant NSCLC, unaffected by line of therapy. Risk stratification had time-dependent prognostic value, with high-risk features transforming into a protective factor for PFS after 6 months. Furmonertinib demonstrated strong intracranial activity (iORR 79.5%). TP53 co-mutation did not confer additional prognostic value in the high-risk subgroup. Furmonertinib was well-tolerated with a favorable safety profile.