氟唑帕利联合安罗替尼治疗一线含铂化疗后广泛期小细胞肺癌的有效性和安全性：一项多中心、单臂、前瞻性 II 期临床研究（STAMP 研究）。
Efficacy and safety of fluzoparib combined with anlotinib in extensive stage small cell lung cancer after first-line platinum-based chemotherapy: a multi-center, single-arm prospective phase II clinical study (STAMP study).
机构信息
Department of Medical Oncology, Provincial Clinical College, Fujian Medical University, Fujian Provincial Hospital, NO.134 Dongjie Street, Fuzhou, 350001, Fujian, China.
Department of Thoracic Oncology, College of Clinical Medicine for Oncology, Fujian Medical University, Fujian Cancer Hospital, NO.420 Fuma Road, Fuzhou, Fujian, 350000, China.
出版信息
BMC Cancer. 2023 Aug 14;23(1):753. doi: 10.1186/s12885-023-11230-5.
BACKGROUND
Small-cell lung cancer (SCLC) is a highly aggressive and lethal malignancy that accounts for 10-15% of lung cancers, and it is generally divided into limited and extensive stage. The standard of care for patients with newly diagnosed extensive-stage SCLC (ES-SCLC) is still platinum-based chemotherapy and as maintenance therapy scheme. Although most parts of patients experience a significant tumor response to first-line therapy, the disease recurs invariably. Anlotinib hydrochloride, a novel oral multitarget tyrosine kinase inhibitor, has significant inhibitory activity against angiogenesis-related kinases, such as VEGFR, FGFR, PDGFR, and c-Kit kinase associated with tumor cell proliferation. Fluzoparib is a type of inhibitor of poly ADP ribose polymerase (PARP, including PARPl, PARP2 and PARP3). Previous studies have shown that Fluzoparib has a strong inhibitory effect on PARP1 activity at the molecular and cellular levels.
METHODS
This is a multi-center, prospective, single-arm phase II clinical study. A total of 50 ES-SCLC patients who experienced disease progression after first-line standard platinum-based chemotherapy with/without immune checkpoint inhibitors scheme, or within 6 months after the completion of treatment will be recruited. Those who had prior treatment with any PARP inhibitor or antiangiogenic agent includes anlotinib, bevacizumab, sorafenib, and thalidomide are excluded. Eligible patients will receive oral anlotinib 8 mg once daily and oral fluzoparib 150 mg twice daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR).
DISCUSSION
The addition of fluzoparib to anlotinib is expected to increase the clinical benefit in ES-SCLC patients after platinum-based chemotherapy.
TRIAL REGISTRATION
This study protocol was prospectively registered on June 17, 2021.
CLINICALTRIALS
gov Identifier: NCT04933175 .
背景
小细胞肺癌（SCLC）是一种高度侵袭性和致命性的恶性肿瘤，约占肺癌的 10-15%，通常分为局限期和广泛期。新诊断的广泛期小细胞肺癌（ES-SCLC）患者的标准治疗方法仍是铂类为基础的化疗，并作为维持治疗方案。尽管大多数患者对一线治疗有明显的肿瘤反应，但疾病仍会不可避免地复发。盐酸安罗替尼是一种新型的口服多靶点酪氨酸激酶抑制剂，对血管生成相关激酶（如 VEGFR、FGFR、PDGFR 和与肿瘤细胞增殖相关的 c-Kit 激酶）具有显著的抑制活性。氟唑帕利是一种聚 ADP 核糖聚合酶（PARP，包括 PARP1、PARP2 和 PARP3）抑制剂。先前的研究表明，氟唑帕利在分子和细胞水平上对 PARP1 活性具有很强的抑制作用。
方法
这是一项多中心、前瞻性、单臂 II 期临床研究。共招募 50 例在一线标准铂类化疗联合/或不联合免疫检查点抑制剂方案治疗后或治疗结束后 6 个月内疾病进展的 ES-SCLC 患者。排除先前接受过任何 PARP 抑制剂或抗血管生成药物（包括安罗替尼、贝伐珠单抗、索拉非尼和沙利度胺）治疗的患者。符合条件的患者将接受每日一次口服安罗替尼 8mg 和每日两次口服氟唑帕利 150mg，直至疾病进展或出现不可耐受的毒性。主要终点是客观缓解率（ORR）。
讨论
在铂类化疗后，氟唑帕利联合安罗替尼有望增加 ES-SCLC 患者的临床获益。
试验注册
本研究方案于 2021 年 6 月 17 日前瞻性注册。
临床试验
gov 标识符：NCT04933175。
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