胃癌治療國(guó)際高峰論壇 更多 >>
- 胃癌藥物臨床試驗(yàn)對(duì)比--愛(ài)斯萬(wàn)?的優(yōu)勢(shì)
- S-1治療中國(guó)晚期胃癌患者的多中心臨床研究報(bào)告（SC-101）
- 有愛(ài)有未來(lái)-愛(ài)斯萬(wàn)?中國(guó)上市會(huì)紀(jì)實(shí)
- 胃癌治療國(guó)際高峰論壇 會(huì)議通知
- 東西方胃癌治療的差異
- 會(huì)議專家簡(jiǎn)介：管忠震教授
- S-1單藥對(duì)比S-1/CDDP聯(lián)合對(duì)比5-FU/CDDP聯(lián)合治療 ...
- StageII/III胃癌根治術(shù)后S-1單藥輔助化療對(duì)比單純手術(shù)治療的III期隨機(jī)臨床試驗(yàn)
Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer.
發(fā)布日期：2009-09-29 17:34 文章來(lái)源：丁香園
分享到： 收藏夾 新浪微博 騰訊微博 開(kāi)心網(wǎng) 豆瓣社區(qū) 人人網(wǎng)
關(guān)鍵詞： Olaparib
ASCO
點(diǎn)擊次數(shù)：
A. Tutt, M. Robson, J. E. Garber, S. Domchek, M. W. Audeh, J. N. Weitzel, M. Friedlander, J. Carmichael
Background: Olaparib (AZD2281; KU-0059436) is a novel, orally active PARP inhibitor that induces synthetic lethality in homozygous BRCAdeficient cells. A phase I trial identified 400 mg bd as the maximum tolerated dose (MTD) with an initial signal of efficacy in BRCA-deficient ovarian cancers (ASCO 2008; abst 5510). The primary aim of this study was to test the efficacy of olaparib in confirmed BRCA1/BRCA2 carriers with advanced refractory breast cancer. The secondary aim was to assess safety and tolerability in this population.
Methods: In an international, multicenter, proof-of-concept, single-arm, phase II study, two sequential patient (pt) cohorts received continuous oral olaparib in 28-day cycles initially at the MTD, 400 mg bd (27 pts), and subsequently at 100 mg bd, a previously identified PARP inhibitory dose (27 pts). Eligibility criteria included confirmed BRCA1/BRCA2 mutation and recurrent, measurable chemotherapy-refractory breast cancer. The primary efficacy endpoint was best objective response rate (ORR; RECIST) post baseline. Progression-free survival (PFS) and clinical benefit rate were secondary endpoints. All adverse events were reported using CTCAE v3.
Results: On November 20, 2008, 54 pts exposed to a median of three prior lines of chemotherapy had been enrolled. 27 pts were dosed at 400 mg bd (18 BRCA1 deficient and 9 BRCA2 deficient), and 24 of these had databased RECIST assessments. The ORR (currently based on unconfirmed responses) was 38% (9/24) (400 mg bd). Causally-related toxicity was mainly mild (grade 1–2) in severity; 9/27 pts (33%) had fatigue; 7/27 (26%) had nausea; 4/27 (15%) had vomiting; and 1/27 (4%) had anemia. Causally-related grade 3 or higher toxicities were seen in 5 pts (19%) with fatigue (3 pts), nausea (2 pts), and anemia (1 pt). 27 pts were treated in the subsequent 100 mg bd cohort where no data are currently available.
Conclusions: Olaparib at 400 mg bd is well tolerated and highly active in advanced chemotherapy refractory BRCA-deficient breast cancer. Toxicity in BRCA1/BRCA2 carriers was similar to that reported previously in non-carriers. This first study with olaparib in BRCA-deficient breast cancers provides positive proof of concept for high activity and tolerability of a genetically defined targeted therapy.
編輯: ludongcn 作者:丁香園通訊員
以下網(wǎng)友留言只代表網(wǎng)友個(gè)人觀點(diǎn)，不代表網(wǎng)站觀點(diǎn)
