TY - JOUR
T1 - Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix
T2 - A phase I clinical experience
AU - Hou, Ming Mo
AU - Liu, Xiaochun
AU - Wheler, Jennifer
AU - Naing, Aung
AU - Hong, David
AU - Coleman, Robert L.
AU - Tsimberidou, Apostolia
AU - Janku, Filip
AU - Zinner, Ralph
AU - Lu, Karen
AU - Kurzrock, Razelle
AU - Fu, Siqing
PY - 2014
Y1 - 2014
N2 - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
KW - Cervical cancer
KW - Matched therapy
KW - PIK3CA mutation
KW - PTEN loss
KW - Phase i trial
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U2 - 10.18632/oncotarget.2584
DO - 10.18632/oncotarget.2584
M3 - Article
C2 - 25426553
AN - SCOPUS:84917710610
SN - 1949-2553
VL - 5
SP - 11168
EP - 11179
JO - Oncotarget
JF - Oncotarget
IS - 22
ER -