Corr Bradley R, Thomas Samantha M, Haight Paulina J, Stock Elizabeth, Floyd Jessica, Borden Lindsay E, Tunnage Irina, Secord Angeles Alvarez, Arend Rebecca, Jackson Amanda L, Wright Jason D, Konecny Gottfried, Castellano Tara, Ko Emily, Podwika Sarah, Backes Floor, Spinosa Daniel, Mullen Margaret, Washington Christina, Pothuri Bhavana, Smitherman Carson, Harsono Alfonsus Adrian Hadikusumo, Khadraoui Hanaa, Suzuki Yukio, Salani Ritu, Powell Kristina, Subbarao Shalini, Gaillard Stephanie
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado Health Cancer Center, Aurora, CO, USA.
Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Durham, NC, United States of America.
Gynecol Oncol. 2025 Oct;201:69-75. doi: 10.1016/j.ygyno.2025.08.008. Epub 2025 Aug 14.
KEYNOTE-775 defined lenvatinib/pembrolizumab as the new standard-of-care for patients with proficient mismatch repair (pMMR) recurrent EC. However, the regimen required dose reductions in 66.5 % of participants and the generalizability of these results was uncertain. We conducted an observational study to determine the prescribing patterns, outcomes and side effects in a real-world setting.
A national multidisciplinary consortium was utilized to study treatment patterns of patients with advanced/recurrent EC treated with lenvatinib/pembrolizumab from 2019 through 2022. Treatment decisions were based on the physician's recommendation.
188 patients across 14 institutions were included. Histologic subtypes were 33 % endometrioid, 41 % serous, 9.6 % mixed, 10.1 % carcinosarcoma, and 2.1 % clear cell. 85.6 % were pMMR and 5.3 % were dMMR. Lenvatinib starting dose was 20 mg in 19.7 %, 18 mg in 14.9 %, 14 mg in 47.3 %, and 10 mg in 18.1 %. Median dose intensity of lenvatinib was 14 mg. Pembrolizumab dosing was 200 mg Q3W in 94.1 %. Grade ≥ 3 adverse events (AE) rates related to lenvatinib were similar across starting doses: 20 mg (13.5 %), 18 mg (17.9 %), 14 mg (7.9 %), 10 mg (17.6 %) (p = 0.31). Response rates in relation to lenvatinib starting dose were 20 mg (27 %), 18 mg (35.7 %), 14 mg (39.3 %), 10 mg (44.1 %) (p = 0.50). In relation to lenvatinib starting dose, PFS, OS and duration of therapy were not statistically different. Response rates (p = 0.24), PFS (p = 0.66) & OS (p = 0.22) were similar in White and Black patients.
In a real-world analysis, the predominant starting dose was 14 mg lenvatinib and 200 mg pembrolizumab. Starting at varying doses does not appear to compromise response rates or survival and no new severe adverse events emerged.
KEYNOTE-775试验将乐伐替尼/帕博利珠单抗定义为错配修复功能正常（pMMR）的复发性子宫内膜癌（EC）患者的新护理标准。然而，该方案在66.5%的参与者中需要降低剂量，且这些结果的可推广性尚不确定。我们进行了一项观察性研究，以确定真实世界环境中的用药模式、结局和副作用。
利用一个全国性多学科联盟研究2019年至2022年期间接受乐伐替尼/帕博利珠单抗治疗的晚期/复发性EC患者的治疗模式。治疗决策基于医生的建议。
纳入了14家机构的188例患者。组织学亚型为子宫内膜样癌33%、浆液性癌41%、混合性癌9.6%、癌肉瘤10.1%、透明细胞癌2.1%。85.6%为pMMR，5.3%为错配修复缺陷（dMMR）。乐伐替尼起始剂量为20mg的占19.7%，18mg的占14.9%，14mg的占47.3%，10mg的占18.1%。乐伐替尼的中位剂量强度为14mg。94.1%的患者帕博利珠单抗给药方案为每3周200mg。不同起始剂量的乐伐替尼相关≥3级不良事件（AE）发生率相似：20mg（13.5%）、18mg（17.9%）、14mg（7.9%）、10mg（17.6%）（p = 0.31）。与乐伐替尼起始剂量相关的缓解率分别为20mg（27%）、18mg（35.7%）、14mg（39.3%）、10mg（44.1%）（p = 0.50）。与乐伐替尼起始剂量相关的无进展生存期（PFS）、总生存期（OS）和治疗持续时间无统计学差异。白人和黑人患者的缓解率（p = 0.24）、PFS（p = 0.66）和OS（p = 0.22）相似。
在一项真实世界分析中，乐伐替尼的主要起始剂量为14mg，帕博利珠单抗为200mg。不同起始剂量似乎并不影响缓解率或生存率，也未出现新的严重不良事件。
