Department of Medical Oncology, Sarah Cannon Cancer Research Institute/Tennessee Oncology, PLLC, Nashville, Tennessee.
Latvian Oncology Centre, Riga East University Hospital, Riga, Latvia.
J Thorac Oncol. 2021 Sep;16(9):1570-1581. doi: 10.1016/j.jtho.2021.03.012. Epub 2021 Apr 3.
Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, an atypical Notch ligand expressed in SCLC tumors. We evaluated the efficacy of Rova-T versus placebo as maintenance therapy in patients with extensive-stage-SCLC after platinum-based chemotherapy.
MERU was a phase 3 randomized, double-blinded, placebo-controlled study. Patients without disease progression after four cycles of platinum-based, front-line chemotherapy were randomized in a 1:1 ratio to receive 0.3 mg/kg Rova-T or placebo (every 6 wk, omitted every third cycle). Primary efficacy end points were progression-free survival (PFS) evaluated by the Central Radiographic Assessment Committee and overall survival (OS) in patients with DLL3-high tumors.
Median age of all randomized patients (N = 748) was 64 years; 78% had TNM stage IV disease. At futility analysis of the subset with DLL3-high tumors, the hazard ratio for OS was 1.07 (95% confidence interval: 0.84-1.36) favoring the placebo arm, with median OS of 8.5 and 9.8 months in the Rova-T and placebo arms, respectively; futility criteria were met. Rova-T significantly improved PFS versus placebo by investigator assessment (4.0 versus 1.4 mo, hazard ratio = 0.48, p < 0.001). Any-grade adverse events (≥20%) in the Rova-T arm were pleural effusion (27%), decreased appetite (27%), peripheral edema (26%), photosensitivity reaction (25%), fatigue (25%), nausea (22%), and dyspnea (21%).
Because of the lack of survival benefit in the Rova-T arm, the study did not meet its primary end point and was terminated early. As a result, the Central Radiographic Assessment Committee evaluation of PFS was not performed. The frequency of grade greater than or equal to 3 and drug-related toxicities were higher with Rova-T versus placebo. Rova-T was associated with unique toxicities, such as pleural and pericardial effusions, photosensitivity reaction, and peripheral edema, which should be carefully considered in the population with extensive-stage-SCLC.
罗瓦替西单抗（Rova-T）是一种针对 DLL3 的抗体药物偶联物，DLL3 是小细胞肺癌（SCLC）肿瘤中表达的一种非典型 Notch 配体。我们评估了 Rova-T 与安慰剂作为铂类化疗后广泛期 SCLC 患者的维持治疗的疗效。
MERU 是一项 3 期随机、双盲、安慰剂对照研究。在完成铂类一线化疗的四个周期后无疾病进展的患者以 1:1 的比例随机分配，接受 0.3 mg/kg Rova-T 或安慰剂（每 6 周一次，每 3 个周期停用一次）。主要疗效终点是中央放射评估委员会评估的无进展生存期（PFS）和 DLL3 高肿瘤患者的总生存期（OS）。
所有随机患者（N=748）的中位年龄为 64 岁；78%的患者为 TNM 分期 IV 期。在 DLL3 高肿瘤亚组的无效性分析中，OS 的风险比为 1.07（95%置信区间：0.84-1.36），安慰剂组更有利，Rova-T 组和安慰剂组的中位 OS 分别为 8.5 个月和 9.8 个月；达到无效性标准。Rova-T 组与安慰剂组相比，经研究者评估的 PFS 显著改善（4.0 个月比 1.4 个月，风险比为 0.48，p<0.001）。Rova-T 组发生率≥20%的任何级别不良事件为胸腔积液（27%）、食欲下降（27%）、外周水肿（26%）、光敏反应（25%）、乏力（25%）、恶心（22%）和呼吸困难（21%）。
由于 Rova-T 组无生存获益，研究未能达到主要终点，提前终止。因此，未进行中央放射评估委员会评估的 PFS。Rova-T 组的 3 级及以上不良反应和药物相关毒性的发生率高于安慰剂组。Rova-T 与独特的毒性相关，如胸腔积液和心包积液、光敏反应和外周水肿，在广泛期 SCLC 患者中应谨慎考虑。
