US Oncology Research, The Woodlands, TX, USA.
Multicentre Italian Trials in Ovarian Cancer and Gynaecological Malignancies Group and Scientific Directorate and Department of Women and Child Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Lancet Oncol. 2021 May;22(5):609-619. doi: 10.1016/S1470-2045(21)00056-5. Epub 2021 Apr 9.
Few effective second-line treatments exist for women with recurrent or metastatic cervical cancer. Accordingly, we aimed to evaluate the efficacy and safety of tisotumab vedotin, a tissue factor-directed antibody-drug conjugate, in this patient population.
This multicentre, open-label, single-arm, phase 2 study was done across 35 academic centres, hospitals, and community practices in Europe and the USA. The study included patients aged 18 years or older who had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); who had received two or fewer previous systemic regimens for recurrent or metastatic disease; had measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1); and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 2·0 mg/kg (up to a maximum of 200 mg) tisotumab vedotin intravenously once every 3 weeks until disease progression (determined by the independent review committee) or unacceptable toxicity. The primary endpoint was confirmed objective response rate based on RECIST (version 1.1), as assessed by the independent review committee. Activity and safety analyses were done in patients who received at least one dose of the drug. This study is ongoing with recruitment completed and is registered with ClinicalTrials.gov, NCT03438396.
102 patients were enrolled between June 12, 2018, and April 11, 2019; 101 patients received at least one dose of tisotumab vedotin. Median follow-up at the time of analysis was 10·0 months (IQR 6·1-13·0). The confirmed objective response rate was 24% (95% CI 16-33), with seven (7%) complete responses and 17 (17%) partial responses. The most common treatment-related adverse events included alopecia (38 [38%] of 101 patients), epistaxis (30 [30%]), nausea (27 [27%]), conjunctivitis (26 [26%]), fatigue (26 [26%]), and dry eye (23 [23%]). Grade 3 or worse treatment-related adverse events were reported in 28 (28%) patients and included neutropenia (three [3%] patients), fatigue (two [2%]), ulcerative keratitis (two [2%]), and peripheral neuropathies (two [2%] each with sensory, motor, sensorimotor, and neuropathy peripheral). Serious treatment-related adverse events occurred in 13 (13%) patients, the most common of which included peripheral sensorimotor neuropathy (two [2%] patients) and pyrexia (two [2%]). One death due to septic shock was considered by the investigator to be related to therapy. Three deaths unrelated to treatment were reported, including one case of ileus and two unknown causes.
Tisotumab vedotin showed clinically meaningful and durable antitumour activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer. Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer.
Genmab, Seagen, Gynaecologic Oncology Group, and European Network of Gynaecological Oncological Trial Groups.
对于复发性或转移性宫颈癌患者，目前有效的二线治疗方法甚少。因此，我们旨在评估 tisotumab vedotin（一种组织因子导向的抗体药物偶联物）在这一患者群体中的疗效和安全性。
这是一项在欧洲和美国的 35 家学术中心、医院和社区实践中进行的多中心、开放性、单臂、2 期研究。该研究纳入了年龄在 18 岁及以上的复发性或转移性鳞状细胞癌、腺癌或腺鳞癌患者；接受贝伐珠单抗联合化疗（如符合当地标准）后疾病进展；既往接受过两线或两线以下复发性或转移性疾病的系统治疗；根据实体瘤反应评估标准（RECIST；版本 1.1）有可测量的疾病；东部肿瘤协作组体力状态为 0 或 1。患者每 3 周接受 2·0 mg/kg（最大 200 mg）tisotumab vedotin 静脉输注，直至疾病进展（由独立审查委员会确定）或不可接受的毒性。主要终点是根据独立审查委员会评估的 RECIST（版本 1.1）确认的客观缓解率。在至少接受过一次药物治疗的患者中进行了疗效和安全性分析。该研究正在进行中，已完成招募，并在 ClinicalTrials.gov 上注册，编号为 NCT03438396。
2018 年 6 月 12 日至 2019 年 4 月 11 日期间共纳入 102 例患者；101 例患者接受了至少一次 tisotumab vedotin 治疗。分析时的中位随访时间为 10·0 个月（IQR 6·1-13·0）。确认的客观缓解率为 24%（95%CI 16-33），包括 7 例（7%）完全缓解和 17 例（17%）部分缓解。最常见的与治疗相关的不良事件包括脱发（38 [38%]例患者）、鼻出血（30 [30%]例）、恶心（27 [27%]例）、结膜炎（26 [26%]例）、疲劳（26 [26%]例）和干眼症（23 [23%]例）。28 例（28%）患者发生了 3 级或更严重的与治疗相关的不良事件，包括中性粒细胞减少症（3 例 [3%]患者）、疲劳（2 例 [2%]患者）、溃疡性角膜炎（2 例 [2%]患者）和周围神经病（2 例 [2%]患者，分别为感觉、运动、感觉运动和周围神经病）。13 例（13%）患者发生了严重的与治疗相关的不良事件，其中最常见的是周围感觉运动神经病（2 例 [2%]患者）和发热（2 例 [2%]患者）。研究者认为，1 例因败血症休克导致的死亡与治疗有关。报告了 3 例与治疗无关的死亡，包括 1 例肠梗阻和 2 例死因不明。
tisotumab vedotin 显示出具有临床意义和持久的抗肿瘤活性，且安全性可管理和耐受，在先前接受过治疗的复发性或转移性宫颈癌患者中。鉴于该患者人群的预后较差，以及当前治疗方法在该人群中的低活性，tisotumab vedotin 如果获得批准，将为复发性或转移性宫颈癌患者提供一种新的治疗选择。
Genmab、Seagen、妇科肿瘤学组和欧洲妇科肿瘤学试验组网络。
