Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.
Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.
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抗肿瘤反应的基线临床预测因素对PARP抑制剂Olaparib在生殖线BRCA1/2突变患有晚期卵巢癌的患者中。
DOI：
10.18632/oncotarget.17005
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发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Yap TA
中科院分区：
文献类型：
--
作者：
Rafii S;Gourley C;Kumar R;Geuna E;Ern Ang J;Rye T;Chen LM;Shapira-Frommer R;Friedlander M;Matulonis U;De Greve J;Oza AM;Banerjee S;Molife LR;Gore ME;Kaye SB;Yap TA
PARP抑制剂olaparib最近获得了美国食品药品监督管理局（FDA）的加速批准，用于晚期BRCA 1/2突变卵巢癌患者。然而，仅在约40%的患者中观察到抗肿瘤应答，基线临床因素对治疗应答的影响仍不清楚。尽管铂敏感性已被认为是对PARP抑制剂反应的标志物，但铂耐药疾病患者仍对奥拉帕尼有反应。纳入108例晚期BRCA 1/2突变卵巢癌患者。使用最近一次铂类化疗结束与PARPi（PTPI）之间的时间间隔预测奥拉帕尼的反应，与铂类敏感性的传统定义无关。铂类药物敏感患者的RECIST完全缓解（CR）和部分缓解（PR）率为35%，铂类药物耐药患者为13%（p<0.005）。与铂类药物敏感性状态无关，PTPI大于52周的患者的RECIST CR/PR率为42%，PTPI小于52周的患者为18%（p=0.016）。未发现基线临床因素（如FIGO分期、减瘤手术、BRCA 1与BRCA 2突变、乳腺癌既往史和乳腺癌既往化疗史）与奥拉帕尼反应之间存在相关性。我们进行了一项国际多中心回顾性研究，以调查来自8个不同癌症中心的晚期BRCA 1/2突变卵巢癌患者的基线临床特征与他们对奥拉帕尼的抗肿瘤反应之间的关系。基于铂敏感性的常规分类，PTPI可用于完善对PARP抑制反应的预测。
The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.
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影响因子：
5.4
作者：
Mateo, J.;Moreno, V.;Molife, L. R.
通讯作者：
Molife, L. R.
影响因子：
45.3
作者：
Fong, Peter C.;Yap, Timothy A.;Kaye, Stan B.
通讯作者：
Kaye, Stan B.
影响因子：
45.3
作者：
Konstantinopoulos, Panagiotis A.;Spentzos, Dimitrios;Cannistra, Stephen A.
通讯作者：
Cannistra, Stephen A.
DOI：
10.1186/bcr3670
发表时间：
2014-06-03
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Watkins JA;Irshad S;Grigoriadis A;Tutt AN
通讯作者：
Tutt AN
影响因子：
168.9
作者：
Audeh, M. William;Carmichael, James;Tutt, Andrew
通讯作者：
Tutt, Andrew