Clinical Research Papers:
Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix: A phase I clinical experience
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Ming-Mo Hou1,4, Xiaochun Liu1, Jennifer Wheler1, Aung Naing1, David Hong1, Robert L. Coleman2, Apostolia Tsimberidou1, Filip Janku1, Ralph Zinner1, Karen Lu2, Razelle Kurzrock3, Siqing Fu1
1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
2Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
3UC San Diego Moores Cancer Center, La Jolla, California
4Division of Hematology-Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
Siqing Fu, e-mail: email@example.com
Keywords: Cervical Cancer, Phase I Trial, Matched Therapy, PIK3CA mutation, PTEN loss
Received: July 21, 2014 Accepted: October 09, 2014 Published: October 29, 2014
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.
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