Oncotarget

Clinical Research Papers:

Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix: A phase I clinical experience

Ming-Mo Hou _, Xiaochun Liu, Jennifer Wheler, Aung Naing, David Hong, Robert L. Coleman, Apostolia Tsimberidou, Filip Janku, Ralph Zinner, Karen Lu, Razelle Kurzrock and Siqing Fu

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Oncotarget. 2014; 5:11168-11179. https://doi.org/10.18632/oncotarget.2584

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Abstract

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

Correspondence to:

Siqing Fu, e-mail: siqingfu@mdanderson.org

Keywords: Cervical Cancer, Phase I Trial, Matched Therapy, PIK3CA mutation, PTEN loss

Received: July 21, 2014     Accepted: October 09, 2014     Published: October 29, 2014

ABSTRACT

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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