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5588 Background: The advent of immunotherapy combined with multitargeted tyrosine kinase inhibitors has significantly improved the treatment of platinum-resistant endometrial cancer (EC). The phase three 309–KEYNOTE-775 trial demonstrated a survival benefit with lenvatinib/pembrolizumab in patients with mismatch repair-proficient (pMMR) advanced EC. However, lenvatinib was discontinued in 31% of patients and dose reduced in 67% due to adverse events (AE). Retrospective reports suggest that reduced dosing for lenvatinib may result in fewer dose reductions, longer time to treatment-related toxicity, and better tolerability without compromising effectiveness. Methods: This multisite, retrospective, cohort study evaluated various dosing strategies of lenvatinib in Kaiser Permanente (KP) California patients treated with lenvatinib/pembrolizumab for pMMR advanced EC between September 1, 2019 and June 30, 2023, and followed through end of membership, December 31, 2023, or death, whichever occurred first. Patients were grouped based on their initial lenvatinib dose: 20 mg daily (Group 1), <20 mg daily (Group 2), and 20 mg daily 5 of 7 days per week (Group 3). The primary outcome was 6-month progression-free survival (PFS); secondary outcomes included incidence rate of lenvatinib dose discontinuation or dose reduction due to AE. Primary analysis of outcomes was performed between Groups 1 and 2; Group 3 was described but not compared to other groups due to small sample size. Results: A total of 369 patients were included in this study (Group 1, n=204; Group 2, n=154; Group 3, n=11). Baseline characteristics were similar between all three groups with mean age of 66.6 ± 9 years; mean body mass index of 29.6 ± 8 kg/m 2 ; and median number of prior lines of systemic therapy of 1 (IQR 1-2). There was no difference in PFS at 6 months between Groups 1 and 2 (40.2% and 33.8%, respectively; p=0.26). There was no difference between Groups 1 and 2 in the rate of lenvatinib discontinuation due to AE (7.2 and 6.6, respectively, per 100 person-year; p=0.61). However, a significantly higher incidence in dose reduction was found in Group 1 when compared to Group 2 (28.1 vs 14.3 per 100 person-year; p<0.01). Conclusions: A lower lenvatinib starting dose (<20 mg daily) in combination with pembrolizumab was no different to the FDA-approved daily dose of 20 mg for the treatment of advanced EC with respect to 6-month PFS. In addition, those who received a lower starting dose experienced fewer dose reductions but no difference in dose discontinuation due to AE. Prospective studies of dose and schedule are needed to confirm these findings and define an optimal dosing strategy.
Ta et al. (Sat,) studied this question.