Clinical Trials for Metastatic Endometrial Cancer

Treatment of advanced metastatic cancers may benefit from the information provided by genomic testing. In "Connie"’s case, tumor subtyping opened up a new line of therapy and new hope.

About "Connie"

In this molecular profile, our fictional patient, Connie, is a 61 year-old woman who noticed that she was getting progressively weak over a period of a few months. She had noticed some irregular vaginal bleeding but thought that this was just part of the “change.” Upon evaluation by her physician, she was found to be profoundly anemic. Further evaluation showed a large endometrial cancer which had metastasized. She initially responded to first-line therapy with carboplatin plus paclitaxel. Several months after initial treatment, however, her tumor has progressed.

Her physician subtyped her tumor using further molecular testing, revealing a PIK3CA mutation and a PTEN deletion.

Rather than agreeing to further chemotherapy which typically has a lesser chance of working as a second line regimen, Connie was alerted to an ongoing clinical trial for which she might be eligible on the basis of the results of the test.

Actionable Information

• Somatic mutations of PIK3CA have been detected in ~30% of endometrial carcinomas. The H1047R mutation is the most common of these mutations accounting for ~30% of PIK3CA mutations in these cancers
• Mutations and deletions of the PTEN tumor suppressor gene are the most common genetic change yet found in endometrial adenocarcinoma, with estimates of the mutational rate ranging from 34-83%
• Mutations in the PIK3CA and PTEN genes lead to frequent activation of PI3K pathway signaling in endometrial cancer, making this pathway an attractive target for therapy in these tumors. Several trials are currently ongoing with agents targeting this pathway.

References

1. Katsutoshi Oda, David Stokoe, Yuji Taketani, et al. High frequency of Coexistent Mutations of PIK3CA and PTEN genes in Endometrial Carcinoma. Cancer Res 2005;65:10669-10673.
2. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JPA, Lees J et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000; 92:924-930.
3. ClinicalTrials.gov accessed 9/15/2011

Note: This fictional, composite story, which includes data from actual representative patient cases, conveys how information from comprehensive genomic testing may impact treatment for management and care of people suffering from cancer.