Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix: A phase I clinical experience.
Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix: A phase I clinical experience.
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DOI：
10.18632/oncotarget.2584
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发表时间：
2014-11-30
期刊：
影响因子：
--
通讯作者：
Fu S
中科院分区：
文献类型：
--
作者：
Hou MM;Liu X;Wheler J;Naing A;Hong D;Coleman RL;Tsimberidou A;Janku F;Zinner R;Lu K;Kurzrock R;Fu S
活化的PI3K/AKT/mTOR通路在转移性或复发性宫颈癌中经常发生。然而，匹配疗法（一种针对特定突变异常的治疗方法）的临床益处尚未确定。我们分析了2006年1月至2013年6月期间接受PIK3CA突变和/或PTEN缺失/突变检测并接受≥1个I期治疗方案的转移性或复发性宫颈癌患者的结果。腺癌患者PIK3CA突变较少（14%），存活时间较鳞状细胞癌患者（48%和7.2个月，p分别= 0.016和0.001）更长（中位14.2个月）。针对活化的PI3K/AKT/mTOR通路的匹配治疗导致SD≥6个月/CR/PR的有利率（53%），并且显着延长无进展生存期（中位，6.0个月），而非匹配治疗（分别为11%和1.5个月，p = 0.08和0.026）。在宫颈鳞状细胞癌患者中，PIK3CA突变的存在与PIK3CA突变不存在（中位数，4.2个月；p = 0.019）相比，总生存期（中位数，9.4个月）明显更长。针对活化的PI3K/AKT/mTOR通路的匹配治疗提供了有意义的临床益处。因此，进一步评估PI3K/AKT/mTOR通路靶向治疗是必要的，特别是在转移性或复发性鳞状细胞癌中。
Activated PI3K/AKT/mTOR pathway frequently occurs in metastatic or recurrent cervical carcinomas. However, the clinical benefits of matched therapy, a therapeutic approach targeting a specific mutational abnormality, have not yet been established. We analyzed the outcomes of patients with metastatic or recurrent cervical carcinomas who had a test for PIK3CA mutation and/or PTEN loss/mutation, and received ≥1 phase I therapeutic regimen between January 2006 and June 2013. Patients with adenocarcinoma had fewer PIK3CA mutations (14%), and survived longer (median, 14.2 months) than those with squamous cell carcinoma (48% and 7.2 months; p = 0.016, and 0.001, respectively). Matched therapy targeting the activated PI3K/AKT/mTOR pathway led to a favorable rate of SD ≥ 6 months/CR/PR (53%) and significantly longer progression-free survival (median, 6.0 months) than non-matched therapy (11% and 1.5 months; p = 0.08 and 0.026; respectively). In patients with squamous cell carcinoma of the cervix, the presence of PIK3CA mutations was associated with a significantly longer overall survival (median, 9.4 months) than the absence of PIK3CA mutations (median, 4.2 months; p = 0.019). Matched therapy targeting the activated PI3K/AKT/mTOR pathway provided meaningful clinical benefits. Thus, further evaluation of PI3K/AKT/mTOR pathway targeted therapy is warranted, especially in metastatic or recurrent squamous cell carcinoma.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
11.2
作者：
Janku F;Wheler JJ;Naing A;Falchook GS;Hong DS;Stepanek VM;Fu S;Piha-Paul SA;Lee JJ;Luthra R;Tsimberidou AM;Kurzrock R
通讯作者：
Kurzrock R
DOI：
10.1056/nejmoa1309748
发表时间：
2014-02-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Tewari KS;Sill MW;Long HJ 3rd;Penson RT;Huang H;Ramondetta LM;Landrum LM;Oaknin A;Reid TJ;Leitao MM;Michael HE;Monk BJ
通讯作者：
Monk BJ
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
3.3
作者：
Eijsink, Jasper J. H.;Noordhuis, Maartje G.;van der Zee, Ate G. J.
通讯作者：
van der Zee, Ate G. J.