Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression. The primary end point was progression-free survival (PFS). Results Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017), which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319). Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade ≥ 3 adverse event (AE; nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those receiving nintedanib versus 17.1% of those in the placebo group. Conclusion Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were manageable. The clinical benefit was evident in patients with epithelioid histology. The confirmatory phase III part of the study is ongoing.

中文翻译：

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尼达尼布联合培美曲塞/顺铂治疗恶性胸膜间皮瘤：随机、安慰剂对照 LUME-Meso 试验的 II 期结果

目的 LUME-Meso 是一项 II/III 期随机、双盲试验，旨在评估尼达尼布联合化疗作为恶性胸膜间皮瘤 (MPM) 一线治疗的有效性和安全性。此处报告了 II 期结果。患者和方法 根据组织学（上皮样或双相）分层的不可切除的非肉瘤样 MPM（东部肿瘤协作组体能状态 0 至 1）的未接受过化疗的患者以 1:1 的比例随机分配至最多 6 个周期的培美曲塞和顺铂加尼达尼布（200 毫克，每天两次）或安慰剂，然后是尼达尼布加安慰剂单药治疗直至进展。主要终点是无进展生存期（PFS）。结果 87 名患者被随机分配。培美曲塞和顺铂周期的中位数为 6；尼达尼布的中位治疗持续时间为 7.8 个月，安慰剂为 5.3 个月。主要 PFS 有利于尼达尼布（风险比 [HR]，0.56；95% CI，0.34 至 0.91；P = .017），这在更新的 PFS 分析中得到证实（HR，0.54；95% CI，0.33 至 0.87；P = . 010)。总体生存率提高的趋势也有利于尼达尼布（HR，0.77；95% CI，0.46 至 1.29；P = .319）。上皮样组织学获益明显，中位总生存期增加为 5.4 个月（HR，0.70；95% CI，0.40 至 1.21；P = .197；中位 [nintedanib 与安慰剂]，20.6 个月与 15.2 个月）和中位 PFS增加 4.0 个月（HR，0.49；95% CI，0.30 至 0.82；P = .006；中位数 [nintedanib 与安慰剂]，9.7 与 5.7 个月）。中性粒细胞减少是最常见的 ≥ 3 级不良事件（AE；尼达尼布 43.2% 与安慰剂 12.2%）；发热性中性粒细胞减少症的发生率很低 (4. 尼达尼布组为 5%，安慰剂组为 0%）。接受尼达尼布治疗的患者中 6.8% 报告了导致停药的 AE，而安慰剂组为 17.1%。结论 在培美曲塞加顺铂中加入尼达尼布可改善 PFS。AE 是可控的。具有上皮样组织学的患者的临床益处是明显的。该研究的验证性 III 期部分正在进行中。