47IN - The impact of targeted therapy in cervical and endometrial cancer

Date 28 September 2014
Event ESMO 2014
Session Targeted therapy in gynaecological cancer
Topics Anti-Cancer Agents & Biologic Therapy
Endometrial Cancer
Cervical Cancer
Translational Research
Presenter Ana Oaknin
Citation Annals of Oncology (2014) 25 (suppl_4): iv18-iv19. 10.1093/annonc/mdu300
Authors A. Oaknin
  • Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES

Abstract

Body

Abstract:

Endometrial (EC) and Cervical Cancer (CC) are the most common gynecological tumors. Although the majority of EC are diagnosed when localized to the uterus, up to 25% of cases recur. In CC the risk of recurrence is 10–20% in early stages and up 70% in locally advanced cases. Unfortunately, in these gynecologic tumors, the systemic therapies are limited in efficacy for recurrent and metastatic disease and new therapies are in need. Increasing understanding of molecular biology is enabling the development of new therapies, which target pathways crucial to tumor proliferation. The most promising targeted therapies including the PI3K/AKT/mTOR pathway and angiogenesis inhibition. The PI3K pathway is often deregulated in gynecologic cancer (PIK3CA mutations up to 33% of CC; 39% of EC) and is highly druggable leading the development of large number of agents. The rapamycin analogs (rapalogs) directly bind and inhibit mTORC1. From more than a half dozen clinical trials of the rapalogs as single agents, it can be concluded that rapalogs have a modest antitumor activity in EC. Objective response rates range from 0%–30% depending upon the clinical population. A molecular biomarker that predicts the clinical benefit of rapalogs has yet to be identified. In CC results of a phase II study of single-agent temsirolimus have recently been reported showing disappointing results. Newer PI3K pathway agents, including pan-PI3K, dual PI3K/mTOR, AKT, and catalytic mTOR inhibitors are being tested in EC. Angiogenesis plays a significant role in tumor progression and an association between VEGF over-expression and poorer prognosis has been established in these both gynecologic tumors. Bevacizumab, a humanized monoclonal antibody against VEGF has clinical activity as single agent in recurrent disease in both tumors. Apart, incorporating Bevacizumab to first line chemotherapy for metastatic or recurrent CC improves overall survival compared to chemotherapy alone in this poor prognosis patients, leading a new standard of care. Phase II studies based on other antiangionenic therapies as multitargeted tyrosine-kinase inhibitors (Sorafenib, Sunitinib, Pazopanib) and VEGF-Trap have shown a modest activity . We should try to identify and develop new target therapies to improve the outcomes in these malignancies.

Disclosure:

The author has declared no conflicts of interest.