Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/Gynecologic Oncology Group study
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Authors
Myers, Andrea P.Filiaci, Virginia L.
Zhang, Yuping
Pearl, Michael
Behbakht, Kian
Makker, Vicky
Hanjani, Parviz
Zweizig, Susan
Burke, James J. 2nd
Downey, Gordon
Leslie, Kimberly K.
Van Hummelen, Paul
Birrer, Michael J.
Fleming, Gini F.
UMass Chan Affiliations
Department of Obstetrics and GynecologyDocument Type
Journal ArticlePublication Date
2016-04-01Keywords
Female Urogenital Diseases and Pregnancy ComplicationsMaternal and Child Health
Obstetrics and Gynecology
Women's Health
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OBJECTIVE: Rapamycin analogs have reproducible but modest efficacy in endometrial cancer (EC). Identification of molecular biomarkers that predict benefit could guide clinical development. METHODS: Fixed primary tissue and whole blood were collected prospectively from patients enrolled on GOG 248. DNA was isolated from macro-dissected tumors and blood; next-generation sequence analysis was performed on a panel of cancer related genes. Associations between clinical outcomes [response rate (RR) 20%; progression-free survival (PFS) median 4.9months] and mutations (PTEN, PIK3CA, PIK3R1, KRAS, CTNNB1, AKT1, TSC1, TSC2, NF1, FBXW7) were explored. RESULTS: Sequencing data was obtained from tumors of 55 of the 73 enrolled pts. Mutation rates were consistent with published reports: mutations in PTEN (45%), PIK3CA (29%), PIK3R1 (24%), K-RAS (16%), CTNNB1 (18%) were common and mutations in AKT1 (4%), TSC1 (2%), TSC2 (2%), NF1 (9%) and FBXW7 (4%) were less common. Increased PFS (HR 0.16; 95% CI 0.01-0.78) and RR (response difference 0.83; 95% CI 0.03-0.99) were noted for AKT1 mutation. An increase in PFS (HR 0.46; 95% CI 0.20-0.97) but not RR (response difference 0.00, 95% CI -0.34-0.34) was identified for CTNNB1 mutation. Both patients with TSC mutations had an objective response. There were no statistically significant associations between mutations in PIK3CA, PTEN, PIK3R1, or KRAS and PFS or RR. CONCLUSIONS: Mutations in AKT1, TSC1 and TSC2 are rare, but may predict clinical benefit from temsirolimus. CTNNB1 mutations were associated with longer PFS on temsirolimus.Source
Gynecol Oncol. 2016 Apr;141(1):43-8. doi: 10.1016/j.ygyno.2016.02.025. Link to article on publisher's siteDOI
10.1016/j.ygyno.2016.02.025Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42779PubMed ID
27016228Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.ygyno.2016.02.025