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

Ming-Mo Hou1, Xiaochun Liu2, Jennifer Wheler2

  • 1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas. Division of Hematology-Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.

Oncotarget
|November 27, 2014
PubMed
Abstract

Insights

Targeted therapy for the PI3K/AKT/mTOR pathway shows promise in recurrent cervical cancer. This approach offers clinical benefits, particularly for squamous cell carcinoma patients with PIK3CA mutations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The PI3K/AKT/mTOR pathway is frequently activated in metastatic or recurrent cervical carcinomas.
  • Clinical benefits of targeted therapy for this pathway remain to be established.

Purpose of the Study:

  • To evaluate the clinical benefits of matched therapy targeting the PI3K/AKT/mTOR pathway in patients with metastatic or recurrent cervical carcinomas.

Main Methods:

  • Analysis of outcomes in patients with metastatic/recurrent cervical cancer who underwent PIK3CA mutation and/or PTEN loss/mutation testing.
  • Treatment regimens administered between January 2006 and June 2013 were analyzed.

Main Results:

  • Adenocarcinoma patients had fewer PIK3CA mutations (14%) and longer survival (14.2 months) than squamous cell carcinoma patients (48%, 7.2 months).
  • Matched therapy demonstrated a higher rate of stable disease (SD) ≥ 6 months/complete response (CR)/partial response (PR) (53%) and longer progression-free survival (PFS) (6.0 months) compared to non-matched therapy.
  • In squamous cell carcinoma, PIK3CA mutations correlated with significantly longer overall survival (9.4 months vs. 4.2 months).

Conclusions:

  • Targeted therapy for the PI3K/AKT/mTOR pathway offers significant clinical benefits in cervical cancer.
  • Further investigation of this targeted therapy is warranted, especially for metastatic or recurrent squamous cell carcinoma.

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