Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gynecol Oncol. 2021 Jul;162(1):24-31. doi: 10.1016/j.ygyno.2021.04.034. Epub 2021 May 3.
We reviewed our institutional data to evaluate toxicity and efficacy outcomes of pembrolizumab/lenvatinib in recurrent endometrial cancer in a "real-world" clinical setting and to compare the impact of reduced lenvatinib starting dose on outcomes.
Retrospectively, we reviewed toxicity, treatment responses, and survival outcomes of patients with recurrent endometrial cancer who received ≥1 cycle of pembrolizumab/lenvatinib. We compared subgroups based on lenvatinib starting dose (recommended [20 mg] vs reduced [<20 mg]) and histologic type.
We analyzed 70 patients (recommended dose cohort, n = 16; reduced dose cohort, n = 54). The most common starting dose was 14 mg daily. Compared to the reduced dose cohort, the recommended dose cohort had a significantly higher mean number of lenvatinib dose reductions due to side effects (1.1 vs. 0.4; p = 0.003) and significantly shorter median time to treatment toxicity (1.3 vs. 3.7 days; p = 0.0001). Response rates did not differ significantly between the recommended and reduced dose cohorts (28.6% vs. 38.3%, respectively; p = 0.752). Two patients, both in the reduced dose cohort, had complete responses. Patients with carcinosarcoma histology had response and clinical benefit rates of 25% (3 of 12) and 58.3% (7 of 12), respectively. There were no differences between the 2 dose cohorts with respect to progression-free (p = 0.245) or overall survival (p = 0.858).
In clinical practice, a lower starting dose of lenvatinib (14 mg daily) in combination with pembrolizumab was safe and efficacious in recurrent endometrial cancer. The combination produced responses in endometrial carcinosarcomas. Larger studies are required to validate these findings.
我们回顾了机构数据，以评估在“真实世界”临床环境中复发子宫内膜癌患者使用帕博利珠单抗/仑伐替尼的毒性和疗效结果，并比较了降低仑伐替尼起始剂量对结果的影响。
我们回顾性分析了接受至少 1 个周期帕博利珠单抗/仑伐替尼治疗的复发子宫内膜癌患者的毒性、治疗反应和生存结果。我们根据仑伐替尼起始剂量（推荐[20 mg]与降低[<20 mg]）和组织学类型进行了亚组比较。
我们分析了 70 例患者（推荐剂量组，n = 16；降低剂量组，n = 54）。最常见的起始剂量为每日 14 mg。与降低剂量组相比，推荐剂量组因副作用而导致仑伐替尼剂量减少的平均次数明显更高（1.1 次比 0.4 次；p = 0.003），且中位至毒性治疗时间明显更短（1.3 天比 3.7 天；p = 0.0001）。推荐剂量组和降低剂量组的客观缓解率无显著差异（分别为 28.6%和 38.3%；p = 0.752）。降低剂量组中有 2 例患者完全缓解。组织学为癌肉瘤的患者的缓解率和临床获益率分别为 25%（12 例中的 3 例）和 58.3%（12 例中的 7 例）。在无进展生存（p = 0.245）和总生存（p = 0.858）方面，这两个剂量组之间没有差异。
在临床实践中，仑伐替尼（每日 14 mg）起始剂量较低（每日 14 mg）联合帕博利珠单抗治疗复发性子宫内膜癌是安全有效的。该联合方案在子宫内膜癌肉瘤中产生了反应。需要更大规模的研究来验证这些发现。
