Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, Silver Spring, Maryland.
Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2015 Oct 1;21(19):4257-61. doi: 10.1158/1078-0432.CCR-15-0887. Epub 2015 Jul 17.
On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth twice daily until disease progression or unacceptable toxicity. The objective response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/upper respiratory infection, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.
2014 年 12 月 19 日,美国食品药品监督管理局(FDA)批准奥拉帕利胶囊(Lynparza;阿斯利康)用于治疗经三线或三线以上化疗治疗的有害或疑似有害种系 BRCA 突变(gBRCAm)晚期卵巢癌患者。BRACAnalysis CDx(Myriad Genetic Laboratories,Inc.)也同时获得批准。一项国际多中心、单臂试验纳入了 137 名接受过三线或三线以上化疗的可测量 gBRCAm 相关卵巢癌患者。患者接受奥拉帕利 400mg 口服,每日两次,直至疾病进展或不可接受的毒性。在该队列中,客观缓解率(ORR)为 34%,中位缓解持续时间为 7.9 个月。接受奥拉帕利治疗的患者最常见的不良反应(≥20%)为贫血、恶心、疲劳(包括乏力)、呕吐、腹泻、味觉障碍、消化不良、头痛、食欲下降、鼻咽炎/咽炎/上呼吸道感染、咳嗽、关节痛/肌肉骨骼疼痛、肌痛、背痛、皮炎/皮疹和腹痛/不适。骨髓增生异常综合征和/或急性髓系白血病发生在该试验入组的 2%的患者中。