Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study.
Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study.
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DOI：
10.1016/s1470-2045(12)70572-7
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Gershenson DM
中科院分区：
文献类型：
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作者：
Farley J;Brady WE;Vathipadiekal V;Lankes HA;Coleman R;Morgan MA;Mannel R;Yamada SD;Mutch D;Rodgers WH;Birrer M;Gershenson DM
由于低级别浆液性卵巢癌是相对化疗耐药的疾病，本研究评估了丝裂原活化蛋白激酶激酶（MEK-1/2）抑制剂Selumetinib（AZD 6244），并探讨了RAS和RAF家族突变与临床结局之间的相关性。患有复发性低级别浆液性卵巢癌或腹膜癌的女性符合条件，并接受100 mg的Selumetinib。口服，每日两次直至进展或毒性入组妇科肿瘤方案239（NCT 00551070）。这项试验已经完成，我们正在报告结果。本试验的主要终点是检查肿瘤对Selumetinib的反应率。该研究使用所有接受治疗的患者来确定缓解率和总生存期。52例患者在2年内入组。8例患者（15.4%）完全缓解（1例）或部分缓解（7例），34例患者（65%）病情稳定。未发生给药相关死亡。观察到3例4级毒性和46例3级毒性发生在1例以上患者中。观察到的4级毒性为心脏（1）、疼痛（1）和肺部（1）。发生的3级毒性包括胃肠道（13）、皮肤病（9）和代谢（7）。司美替尼耐受性良好，在治疗复发性低级别浆液性癌中具有活性。在探索性分析中，对司美替尼的应答似乎与RAS/RAF突变状态无关。63%的疾病控制是令人鼓舞的，值得进一步评估MEK抑制剂在这一人群中的作用。这项研究是由国家癌症研究所赠款的妇科肿瘤组。
Because low grade serous carcinoma of the ovary is relatively chemo resistant disease, this study evaluated Selumetinib (AZD6244), an inhibitor of mitogen-activated protein kinase kinase (MEK-1/2), and explored associations between RAS, and RAF family mutations with clinical outcome. Women with recurrent low-grade serous ovarian or peritoneal carcinoma were eligible and received Selumetinib at 100 mg. orally b.i.d. until progression or toxicity were enrolled in Gynecologic Oncology protocol 239(NCT00551070). This trial has been completed and we are reporting the results. The primary endpoint of this trial was to examine tumor response rate to Selumetinib. The study used all-treated patients to determine response rate and overall survival. Fifty-two patients were enrolled over two years. Eight patients (15.4%) had complete (1) or partial (7) responses, and 34 (65%) had stable disease. There were no treatment-related deaths. There were three observed grade 4 toxicities and 46 grade 3 toxicities that occurred in more than one patient. Observed grade 4 toxicities were cardiac (1), pain (1), and pulmonary (1). Grade 3 toxicities that occurred included gastrointestinal (13), dermatologic (9), and metabolic (7). Selumetinib is well tolerated, and is active in the treatment of recurrent low-grade serous carcinoma. In exploratory analyses, response to Selumetinib did not appear to be related to RAS/RAF mutational status. The 63% disease control is encouraging and worthy of further evaluation of MEK inhibitors in this population. This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group.