Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma

Brian M Slomovitz; Yunyun Jiang; Melinda S Yates; Pamela T Soliman; Taren Johnston; Maureen Nowakowski; Charles Levenback; Qian Zhang; Kari Ring; Mark F Munsell; David M Gershenson; Karen H Lu; Robert L Coleman

doi:10.1200/JCO.2014.58.3401

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Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma

Journal article

Open access

Peer reviewed

Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma

Brian M Slomovitz, Yunyun Jiang, Melinda S Yates, Pamela T Soliman, Taren Johnston, Maureen Nowakowski, Charles Levenback, Qian Zhang, Kari Ring, Mark F Munsell, …

Journal of clinical oncology, Vol.33(8), pp.930-936

2015-03-10

DOI: https://doi.org/10.1200/JCO.2014.58.3401

PMCID: PMC4348638

PMID: 25624430

Abstract

Immunohistochemistry

Triazoles - administration & dosage

Receptors, Estrogen - metabolism

TOR Serine-Threonine Kinases - metabolism

Humans

Middle Aged

Gene Expression Regulation, Neoplastic

Antineoplastic Agents - administration & dosage

Phosphatidylinositol 3-Kinases - antagonists & inhibitors

Biomarkers, Tumor

Endometriosis - complications

Receptors, Progesterone - metabolism

Nitriles - administration & dosage

Time Factors

DNA Mutational Analysis

Aged, 80 and over

Adult

Female

Everolimus

Immunosuppressive Agents - administration & dosage

Sirolimus - analogs & derivatives

Neoplasm Recurrence, Local

Treatment Outcome

beta Catenin - genetics

Disease-Free Survival

Sirolimus - administration & dosage

Bayes Theorem

Endometrial Neoplasms - drug therapy

Aged

Cohort Studies

The phosphoinositol-3 kinase (PI3K) pathway is frequently dysregulated in endometrial cancer (EC). Hormonal manipulation leads to response in some patients with EC, but resistance derived from PI3K pathway activation has been documented. Targeting mammalian target of rapamycin (mTOR) may overcome endocrine resistance. We conducted a two-institution phase II trial of everolimus and letrozole in women with recurrent EC. Patients were considered incurable, had measurable disease, and were treated with up to two prior cytotoxic regimens. Everolimus was administered orally at 10 mg daily and letrozole was administered orally at 2.5 mg daily. Each cycle consisted of 4 weeks of therapy. Patients were treated until progression, toxicity, or complete response (CR). The primary end point was the clinical benefit rate (CBR), which was defined as CR, partial response, or stable disease (≥ 16 weeks) by RECIST 1.0 criteria. Translational studies were performed to correlate biomarkers with response. Thirty-eight patients were enrolled (median age, 62 years; range, 24 to 82 years). Thirty-five patients were evaluable for response. The CBR was 40% (14 of 35 patients); the median number of cycles among responders was 15 (range, seven to 29 cycles). The confirmed objective response rate (RR) was 32% (11 of 35 patients; nine CRs and two partial responses; median, 15 cycles; range, eight to 29 cycles). Twenty percent of patients (seven of 35 patients) were taken off treatment after a prolonged CR and at the discretion of the treating clinician. None of the patients discontinued treatment as a result of toxicity. Serous histology was the best predictor of lack of response. Patients with endometrioid histology and CTNNB1 mutations responded well to everolimus and letrozole. Everolimus plus letrozole results in a high CBR and RR in patients with recurrent EC. Further development of this combination in recurrent endometrioid EC is under way.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.128 Fertility, Endometriosis & Hysterectomy; 1.128.753 Endometrial Cancer
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma
Creators: Brian M Slomovitz - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Yunyun Jiang - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Melinda S Yates - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Pamela T Soliman - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Taren Johnston - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Maureen Nowakowski - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Charles Levenback - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Qian Zhang - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Kari Ring - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Mark F Munsell - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
David M Gershenson - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Karen H Lu - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL
Robert L Coleman - Brian M. Slomovitz, Yunyun Jiang, Melinda S. Yates, Pamela T. Soliman, Taren Johnston, Charles Levenback, Qian Zhang, Kari Ring, Mark F. Munsell, David M. Gershenson, Karen H. Lu, and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Slomovitz and Maureen Nowakowski, Morristown Medical Center, Morristown, NJ; and Brian M. Slomovitz, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL. rcoleman@mdanderson.org
Publication Details: Journal of clinical oncology, Vol.33(8), pp.930-936
Publisher: United States
Grant note: P50CA098258 / NCI NIH HHS P50 CA098258 / NCI NIH HHS T32 CA101642 / NCI NIH HHS P30 CA016672 / NCI NIH HHS CA016672 / NCI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Dept of Obstetrics & Gynecology
Language: English
Resource Type: Journal article
PMID: 25624430
PMCID: PMC4348638
Record Identifier: 991031578520402976