TY - JOUR
T1 - Everolimus, letrozole, and metformin in women with advanced or recurrent endometrioid endometrial cancer
T2 - A multi-center, single arm, phase II study
AU - Soliman, Pamela T.
AU - Westin, Shannon N.
AU - Iglesias, David A.
AU - Fellman, Bryan M.
AU - Yuan, Ying
AU - Zhang, Qian
AU - Yates, Melinda S.
AU - Broaddus, Russell R.
AU - Slomovitz, Brian M.
AU - Lu, Karen H.
AU - Coleman, Robert L.
N1 - Funding Information:
S.N. Westin is an employee/paid consultant for AstraZeneca, Clovis Oncology, Tesaro, Roche/Genentech, Merck, Pfizer, Takeda, Circulogene, and Novartis, and reports receiving commercial research grants from AstraZeneca, ArQule, Clovis Oncology, Tesaro, Bayer, Roche/Genentech, and Cotinga Pharmaceuticals. Y. Yuan is a paid consultant for Boehringer Ingelheim Pharmaceuticals, Servier Pharmaceuticals, Amgen Inc., Deciphera Pharmaceuticals, Citius Pharmaceuticals, and Midas Medical Technologies. B.M. Slomovitz is a paid consultant for GlaxoSmithKline, Clovis, Genentech, and AstraZeneca. R.L. Coleman reports receiving other commercial research support from Merck, Abbvie, AstraZeneca, Janssen, Clovis, Roche/Genentech, and Novartis. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
This work was supported in part by Cancer Center Support Grant (NCI Grant P30 CA016672), Andrew Sabin Family Fellowship, NCI SPORE in Uterine Cancer (2P50 CA098258-06), and Novartis.
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Purpose: Treatment for patients with recurrent endometrioid endometrial cancer (EEC) are limited as paclitaxel is the only second-line chemotherapy with a response rate >13%. Targeting PIK3/mTOR in combination with hormonal therapy has shown promise. The addition of metformin may enhance this response. We conducted a phase II study evaluating everolimus, letrozole, and metformin in advanced/recurrent EEC. Patients and Methods: A Simon two-stage design was employed. Women with ≤2 prior chemotherapy regimens for recurrence were eligible. Pretreatment biopsy was required, followed by everolimus 10 mg orally, letrozole 2.5 mg orally, and metformin 500 mg orally twice a day on a 4-week cycle. The primary endpoint was clinical benefit (CB), defined as complete response (CR), partial response (PR), or stable disease (SD) confirmed at 16 weeks. Patients were treated until progression or toxicity. Results: Sixty-two patients were enrolled. Median age was 62 years (40–77) with 401 cycles completed, median of 6 cycles (1–31). Fifty-four patients were evaluable for response with a CB rate of 50% (27/54). Best overall response (OR) was PR 28% (15/54) and SD 22% (12/54). Thirteen patients received >12 cycles. Median follow-up was 17.9 months (2–47). Median progression-free survival was 5.7 [95% confidence interval (CI), 3.0–8.1] and OS was 19.6 months (95% CI, 14.2–26.3). Positive progesterone receptor expression was associated with CB (89.5% vs. 27.3%, P ¼ 0.001). Conclusions: Everolimus, letrozole, and metformin resulted in 50% CB and 28% OR in women with recurrent EEC. Progesterone receptor–positive tumors may have better response; validation studies are needed.
AB - Purpose: Treatment for patients with recurrent endometrioid endometrial cancer (EEC) are limited as paclitaxel is the only second-line chemotherapy with a response rate >13%. Targeting PIK3/mTOR in combination with hormonal therapy has shown promise. The addition of metformin may enhance this response. We conducted a phase II study evaluating everolimus, letrozole, and metformin in advanced/recurrent EEC. Patients and Methods: A Simon two-stage design was employed. Women with ≤2 prior chemotherapy regimens for recurrence were eligible. Pretreatment biopsy was required, followed by everolimus 10 mg orally, letrozole 2.5 mg orally, and metformin 500 mg orally twice a day on a 4-week cycle. The primary endpoint was clinical benefit (CB), defined as complete response (CR), partial response (PR), or stable disease (SD) confirmed at 16 weeks. Patients were treated until progression or toxicity. Results: Sixty-two patients were enrolled. Median age was 62 years (40–77) with 401 cycles completed, median of 6 cycles (1–31). Fifty-four patients were evaluable for response with a CB rate of 50% (27/54). Best overall response (OR) was PR 28% (15/54) and SD 22% (12/54). Thirteen patients received >12 cycles. Median follow-up was 17.9 months (2–47). Median progression-free survival was 5.7 [95% confidence interval (CI), 3.0–8.1] and OS was 19.6 months (95% CI, 14.2–26.3). Positive progesterone receptor expression was associated with CB (89.5% vs. 27.3%, P ¼ 0.001). Conclusions: Everolimus, letrozole, and metformin resulted in 50% CB and 28% OR in women with recurrent EEC. Progesterone receptor–positive tumors may have better response; validation studies are needed.
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U2 - 10.1158/1078-0432.CCR-19-0471
DO - 10.1158/1078-0432.CCR-19-0471
M3 - Article
C2 - 31628143
AN - SCOPUS:85079020568
SN - 1078-0432
VL - 26
SP - 581
EP - 587
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 3
ER -