Impact of anti-VEGF therapy duration on KRAS/NRAS WT mCRC survival after anti-EGFR therapy.

Abstract

e15549 Background: First-line anti-EGFR therapy is one of the choice that improves outcomes in KRAS/NRAS wild-type(WT), but evidence on subsequent anti-VEGF therapy following anti-EGFR therapy remains limited. This study evaluated the impact of subsequent anti-VEGF therapy, particularly its duration on treatment outcomes. Methods: A retrospective analysis was conducted on 1,757 mCRC patients. Among them, 1,428 received at least two cycles of systemic therapy, and 629 were confirmed as KRAS/NRAS WT. Of these, 414 received VEGF-based therapy first, while 215 received EGFR-based therapy first. Patients were further classified based on whether they received subsequent anti-VEGF therapy following an initial anti-EGFR regimen. Baseline characteristics, metastatic patterns, and treatment outcomes, including overall survival (OS), were analyzed. Statistical significance was determined using Kaplan-Meier and Cox regression models. Results: Among KRAS/NRAS WT patients, 215 initiated therapy with EGFR-based regimens and 83 with following anti-VEGF and 132 without. Anti-EGFR followed by anti-VEGF (n = 83) achieved an OS of 34.1 months compared to 18.6 months for EGFR alone (n = 132; p = 0.015). Further analysis based on surgical treatment showed that in patients who underwent surgery, the addition of anti-VEGF therapy after anti-EGFR therapy resulted in a numerically longer OS (43.6 months vs. 36.4 months), but the difference was not statistically significant (p = 0.616). However, among patients who did not undergo surgery, those receiving anti-VEGF therapy following anti-EGFR therapy had significantly improved survival compared to those who did not receive anti-VEGF therapy (22.4 months vs. 13.6 months, p = 0.014). A significant positive correlation was observed between the number of subsequent anti-VEGF therapy cycles and OS (R² = 0.87, p < 0.001). Patients receiving more than 10 cycles of subsequent anti-VEGF therapy exhibited a markedly prolonged OS (48.2 months vs. 27.7 months; p = 0.008). In multivariable analysis adjusting for age, tumor location, ECOG performance status, and target therapy, the addition of anti-VEGF therapy following anti-EGFR therapy was associated with a significantly improved prognosis (HR = 0.686, p = 0.042), corresponding to a 31.4% reduction in mortality risk. Furthermore, each additional cycle of anti-VEGF therapy in the subsequent therapy was associated with a 5.2% improvement in OS (HR = 0.948, p = 0.006). Conclusions: Sequential administration of anti-EGFR therapy followed by anti-VEGF therapy significantly improves OS in KRAS/NRAS WT mCRC patients. Notably, prolonged anti-VEGF therapy is associated with superior outcomes, particularly in patients who could not undergo surgical treatment. These findings highlight the significant survival benefit associated with prolonged subsequent anti-VEGF therapy in clinical practice.