Guy's and St Thomas' NHS Foundation Trust, London, UK
START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain.
Int J Gynecol Cancer. 2021 Nov;31(11):1428-1436. doi: 10.1136/ijgc-2021-002881. Epub 2021 Oct 5.
Second-line treatment of endometrial cancer is an unmet medical need. We conducted a phase I study evaluating lurbinectedin and doxorubicin intravenously every 3 weeks in patients with solid tumors. The aim of this study was to characterise the efficacy and safety of lurbinectedin and doxorubicin for patients with endometrial cancer.
Thirty-four patients were treated: 15 patients in the escalation phase (doxorubicin 50 mg/m and lurbinectedin 3.0-5.0 mg) and 19 patients in the expansion cohort (doxorubicin 40 mg/m and lurbinectedin 2.0 mg/m). All histological subtypes were eligible and patients had received one to two prior lines of chemotherapy for advanced disease. Antitumor activity was evaluated every two cycles according to the Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.
Median age (range) was 65 (51-78) years. Eastern Cooperative Oncology Group performance status was up to 1 in 97% of patients. In the escalation phase, 4 (26.7%) of 15 patients had confirmed response: two complete and two partial responses (95% CI 7.8% to 55.1%). Median duration of response was 19.5 months. Median progression-free survival was 7.3 (2.5 to 10.1) months. In the expansion cohort, confirmed partial response was reported in 8 (42.1%) of 19 patients (95% CI 20.3% to 66.5%). Median duration of response was 7.5 (6.4 to not reached) months, median progression-free survival was 7.7 (2.0 to 16.7) months and median overall survival was 14.2 (4.5 to not reached) months. Fatigue (26.3% of patients), and transient and reversible myelosuppression (neutropenia, 78.9%; febrile neutropenia, 21.1%; thrombocytopenia, 15.8%) were the main grade 3 and higher toxicities in the expanded cohort.
In patients with recurrent advanced endometrial cancer treated with doxorubicin and lurbinectedin, response rates (42%) and duration of response (7.5 months) were favorable. Further evaluation of doxorubicin and lurbinectedin is warranted in this patient population.
子宫内膜癌的二线治疗是未满足的医学需求。我们进行了一项 I 期研究，评估了每周静脉注射一次洛布奈丁和多柔比星治疗实体瘤患者。本研究的目的是描述洛布奈丁和多柔比星治疗子宫内膜癌患者的疗效和安全性。
共治疗 34 例患者：15 例在递增阶段（多柔比星 50mg/m2和洛布奈丁 3.0-5.0mg），19 例在扩展队列（多柔比星 40mg/m2和洛布奈丁 2.0mg/m2）。所有组织学亚型均符合条件，患者在晚期疾病中接受了一到两线化疗。根据实体瘤反应评估标准 1.1 每两个周期评估抗肿瘤活性。根据国家癌症研究所常见不良事件术语标准 4.0 对不良事件进行分级。
中位年龄（范围）为 65（51-78）岁。97%的患者东部合作肿瘤学组体能状态为 1 分。在递增阶段，15 例患者中有 4 例（26.7%）有确认的反应：2 例完全缓解和 2 例部分缓解（95%CI 7.8%至 55.1%）。中位缓解持续时间为 19.5 个月。中位无进展生存期为 7.3（2.5 至 10.1）个月。在扩展队列中，19 例患者中有 8 例（42.1%）报告了确认的部分缓解（95%CI 20.3%至 66.5%）。中位缓解持续时间为 7.5（6.4 至未达到）个月，中位无进展生存期为 7.7（2.0 至 16.7）个月，中位总生存期为 14.2（4.5 至未达到）个月。在扩展队列中，主要的 3 级及以上毒性为疲劳（26.3%的患者）和短暂可逆的骨髓抑制（中性粒细胞减少症，78.9%；发热性中性粒细胞减少症，21.1%；血小板减少症，15.8%）。
在接受多柔比星和洛布奈丁治疗的复发性晚期子宫内膜癌患者中，反应率（42%）和缓解持续时间（7.5 个月）均较好。在该患者人群中，进一步评估多柔比星和洛布奈丁是合理的。
