Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA.
Department of Medicine, University of Michigan, Ann Arbor, MI.
Clin Lung Cancer. 2023 Sep;24(6):563-567. doi: 10.1016/j.cllc.2023.04.004. Epub 2023 Apr 7.
: Malignant pleural mesothelioma (MPM) is a disease for which there remains an unmet need for better therapeutic options. Nintedanib is an oral multikinase inhibitor impacting VEGF, FGF, PDGFR, and other kinase activity such as TGFß signaling pathways. We conducted a phase II trial of nintedanib in patients with recurrent MPM.
: Patients with MPM previously treated with platinum-based chemotherapy, performance status (PS) 0–1, adequate organ function, and no contraindications to anti-angiogenic therapy were eligible and were treated with nintedanib 200 mg twice per day until disease progression or unacceptable toxicity. The primary endpoint was 4-month progression-free survival (PFS).
: Twenty patients were enrolled. The median age was 70 years (range 32–81), 90% were male, and 80% were PS 1. The histology was 70% epithelioid, 5% sarcomatoid, 10% biphasic, and 15% unknown. 15% had prior bevacizumab. The median follow-up was 4.1 mo. There were no responses but 40% had stable disease at 8 weeks. The median PFS was 1.8 mo. (95% CI: 1.68, 3.55) and the 4-month PFS rate was 13%. The median OS was 4.2 mo. (95% CI: 2.53, 8.74) and the 4-month OS rate was 55%. Toxicities were primarily grade 1–2 and included diarrhea, fatigue, edema, transaminase elevation, anorexia, nausea, vomiting and dyspnea.
: The activity of nintedanib in previously treated MPM patients was. modest. The trial did not meet its primary PFS endpoint. Even though 2 patients had prolonged stable disease for >4 months, the efficacy of nintedanib remains unproven.
恶性胸膜间皮瘤（MPM）是一种治疗选择有限的疾病。尼达尼布是一种口服多激酶抑制剂，可影响 VEGF、FGF、PDGFR 和其他激酶活性，如 TGFβ 信号通路。我们进行了尼达尼布治疗复发性 MPM 患者的 II 期试验。
先前接受过含铂化疗、表现状态（PS）0-1、器官功能良好且无抗血管生成治疗禁忌证的 MPM 患者符合条件，并接受尼达尼布 200mg，每日两次，直至疾病进展或出现不可接受的毒性。主要终点是 4 个月无进展生存期（PFS）。
共纳入 20 例患者。中位年龄为 70 岁（范围 32-81 岁），90%为男性，80%为 PS 1。组织学类型为 70%上皮样、5%肉瘤样、10%双相型和 15%未知。15%的患者曾接受贝伐珠单抗治疗。中位随访时间为 4.1 个月。无缓解，但 8 周时有 40%的患者疾病稳定。中位 PFS 为 1.8 个月（95%CI：1.68，3.55），4 个月 PFS 率为 13%。中位 OS 为 4.2 个月（95%CI：2.53，8.74），4 个月 OS 率为 55%。毒性主要为 1-2 级，包括腹泻、疲劳、水肿、转氨酶升高、厌食、恶心、呕吐和呼吸困难。
尼达尼布在先前治疗过的 MPM 患者中的活性有限。该试验未达到主要的 PFS 终点。尽管有 2 例患者的稳定疾病持续时间超过 4 个月，但尼达尼布的疗效仍未得到证实。
