Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncologist. 2020 Oct;25(10):e1457-e1463. doi: 10.1634/theoncologist.2020-0610. Epub 2020 Jul 19.
Treatment with the Aurora kinase A inhibitor yields often durable disease control, but limited tumor regression, in heavily pretreated patients with unresectable malignant pleural or peritoneal mesothelioma. In a limited sample size, MYC copy-number gain or gene amplification, a candidate predictive biomarker for alisertib, did not correlate with improved response numbers or patient outcomes.
Malignant mesothelioma is an aggressive disease for which few effective therapies are available. The Aurora family kinases are critical for mitotic fidelity and highly expressed in mesothelioma, wherein their inhibition leads to growth arrest in vitro. We evaluated the efficacy of alisertib, an Aurora A kinase inhibitor, in relapsed malignant mesothelioma.
Twenty-six patients with previously treated, unresectable pleural or peritoneal mesothelioma were enrolled on a single-arm, single-institution phase II trial of alisertib at a dosage of 50 mg twice daily for 7 of every 21 days. The primary endpoint was 4-month disease control rate. Secondary endpoints included overall response rate, progression free survival, overall survival, safety/toxicity, and correlation of endpoints with MYC copy number.
Of the 25 evaluable patients treated on study, 8 (32%) experienced 4-month disease control, surpassing the futility endpoint. There were no confirmed partial or complete responses. Median progression-free and overall survival were 2.8 months and 6.3 months, respectively. No associations between MYC copy number and outcomes were observed.
Alisertib has modest activity in this unselected malignant mesothelioma population. Several patients achieved durable disease control. Although the study did meet its prespecified futility endpoint, the sponsor elected to close the trial at the interim analysis.
在既往治疗过的、无法切除的恶性胸膜或腹膜间皮瘤患者中，使用 Aurora 激酶 A 抑制剂治疗通常可获得持久的疾病控制，但肿瘤缓解有限。在有限的样本量中，作为alisertib 的候选预测生物标志物的 MYC 拷贝数增加或基因扩增与改善的反应数量或患者结局无关。
恶性间皮瘤是一种侵袭性疾病，有效的治疗方法很少。Aurora 家族激酶对于有丝分裂保真度至关重要，在间皮瘤中高度表达，其抑制导致体外生长停滞。我们评估了 Aurora A 激酶抑制剂 alisertib 在复发性恶性间皮瘤中的疗效。
26 例既往治疗过的、无法切除的胸膜或腹膜间皮瘤患者参加了一项单臂、单机构的 alisertib Ⅱ期试验，剂量为 50mg，每日 2 次，每 21 天的 7 天内给药。主要终点是 4 个月疾病控制率。次要终点包括总缓解率、无进展生存期、总生存期、安全性/毒性以及终点与 MYC 拷贝数的相关性。
在 25 例接受研究治疗的可评估患者中，8 例（32%）在 4 个月时疾病得到控制，超过了无效终点。没有确认的部分或完全缓解。中位无进展生存期和总生存期分别为 2.8 个月和 6.3 个月。未观察到 MYC 拷贝数与结局之间的关联。
alisertib 在未选择的恶性间皮瘤人群中具有适度的活性。一些患者获得了持久的疾病控制。尽管该研究确实达到了其预先指定的无效终点，但研究赞助商在中期分析时决定关闭试验。
