Multicenter phase II study of the AKT inhibitor MK-2206 in recurrent or metastatic nasopharyngeal carcinoma from patients in the mayo phase II consortium and the cancer therapeutics research group (MC1079)
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摘要Background This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC). Method Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was measured, and archived tumors were analyzed for the expression of AKT and PIK3CA mutation and PIK3CA amplification. The dual primary endpoint was objective response rate and 6-month progression-free survival (PFS) rate. Results 21 patients were enrolled and one patient achieved a partial response (5 %) and 11 had stable disease (52 %), with a median PFS of 3.5 months (95 % confidence interval, CI: 0.9-7.3). The 6-month PFS rate was 43 % (95 % CI: 22-66 %) and the median OS was 10 months (95 % CI: 5.9 months-not reached). Seven patients (33 %) experienced grade 3 toxicities which could be related to MK-2206. Macular-papular rash was the most common (n = 6), followed by hyperglycemia (n = 2) and fatigue (n = 1). In the 12 tumor samples analyzed, PIK3CA amplification was detected in one patient's primary NPC, who had SD lasting over 12 months. Patients with decreasing EBV DNA values over time were more likely to be alive and progression-free for at least 6 months than those without a decrease (p = 0.001). Conclusion The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors.
著者Ma BBY, Goh BC, Lim WT, Hui EP, Tan EH, Lopes GD, Lo KW, Li L, Loong H, Foster NR, Erlichman C, King AD, Kam MKM, Leung SF, Chan KC, Chan ATC
期刊名稱Investigational New Drugs
出版年份2015
月份8
日期1
卷號33
期次4
出版社Springer Verlag (Germany)
頁次985 - 991
國際標準期刊號0167-6997
電子國際標準期刊號1573-0646
語言英式英語
關鍵詞AKT inhibitor; MK2206; Nasopharyngeal carcinoma; PIK3CA
Web of Science 學科類別Oncology; Pharmacology & Pharmacy

上次更新時間 2020-01-12 於 23:31