Faculty Opinions recommendation of Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer.

2013 ◽  
Author(s):  
David Potter
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
First Line

scholarly journals Phase III Study Comparing Exemestane With Tamoxifen As First-Line Hormonal Treatment of Metastatic Breast Cancer in Postmenopausal Women: The European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group

2008 ◽  
Vol 26 (30) ◽  
pp. 4883-4890 ◽  
Author(s):  
Robert J. Paridaens ◽  
Luc Y. Dirix ◽  
Louk V. Beex ◽  
Marianne Nooij ◽  
David A. Cameron ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Postmenopausal Women ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Hormonal Treatment ◽  
Phase Iii ◽  
Tamoxifen Treatment ◽  
Primary Study ◽  
First Line

Purpose This phase III randomized open-label clinical trial was designed to evaluate the efficacy and safety of the steroidal aromatase inactivator exemestane versus the antiestrogen tamoxifen as first-line treatment for metastatic breast cancer (MBC) in postmenopausal women. Patients and Methods The study was conducted at 81 centers and enrolled postmenopausal patients with measurable hormone-sensitive metastatic or locally advanced breast cancer. Prior adjuvant chemotherapy and/or tamoxifen were allowed. One previous chemotherapy regimen and no prior hormone therapy for advanced disease were permitted. Patients were randomly assigned to receive exemestane 25 mg or tamoxifen 20 mg orally once daily until disease progression or unacceptable toxicity occurred. Results A total of 371 patients enrolled at 79 sites (182 exemestane, 189 tamoxifen) were included in the analysis. Both treatments were generally well tolerated without major toxicity. Overall response rate was greater for exemestane than for tamoxifen treatment (46% v 31%; odds ratio = 1.85; 95% CI, 1.21 to 2.82; P = .005). Median progression-free survival (PFS) was longer with exemestane (9.9 months; 95% CI, 8.7 to 11.8 months) than with tamoxifen (5.8 months; 95% CI, 5.3 to 8.1 months). However, these early differences (Wilcoxon P = .028) did not translate to a longer-term benefit in PFS, the primary study end point (log-rank P = .121). There was also no difference in survival between both study arms. Conclusion Exemestane is an effective and well-tolerated first-line hormonal treatment for postmenopausal women with MBC and offers significant early improvement in time to tumor progression when compared with tamoxifen.

scholarly journals Dutch Breast Cancer Trialists' Group (BOOG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 61-79
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Phase Iii ◽  
List Type ◽  
First Line ◽  
Open Label ◽  
Phase Iii Study

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Dutch breast cancer trialists' group (BOOG). Clinical trials include:An open label randomized (inter)national multicenter comparative trial of 5 years adjuvant endocrine therapy with an LHRH agonist plus an aromatase inhibitor (goserelin + anastrozole) versus five courses FE90C chemotherapy followed by the same endocrine therapy in pre- or perimenopausal patients with hormone receptor-positive primary breast cancer (PRemenopausal Optimal Management IS Endocrine therapy). BOOG 2002-01/PROMISE. ISRCTN23561723Open label, comparative, randomized, multicenter, study of trastuzumab (Herceptin) given with docetaxel (Taxotere) versus sequential single agent therapy with trastuzumab followed by docetaxel as first-line treatment for metastatic breast cancer (MBC) patients with HER2neu overexpression. BOOG 2002-02/HERTAX ISRCTN13770586Micro-metastases and Isolated tumour cells: Robust and Relevant Or Rubbish? The MIRROR study in BREAST CANCER. BOOG 2003-03/ZonMW 3214Radiation dose intensity study in breast cancer in young women: a randomized phase III trial of additional dose to the tumor bed. BOOG 2004-01/Young Boost SRCTN45066831Microarray analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens, a randomized phase III study. MATADOR, BOOG 2005-02, CKTO 2004-04 ISRCTN61893718A prospective randomised, open, multicentre, phase III study to assess different Durations of Anastrozole therapy after 2–3 years Tamoxifen as Adjuvant therapy in postmenopausal women with breast cancer. 2006-01/DATAA randomized, open-label phase III study of first line chemotherapy in elderly metastatic breast cancer patients, comparing intravenous pegylated liposomal doxorubicin with oral capecitabine; and the incorporation of a complete geriatric assessment. 2006-02/OMEGABOOG participation in International studies:. BOOG 2001-01/TEAM trial. BOOG 2001-02/AMAROS (EORTC 10981/22023). BOOG 2002-04/HERA (BIG 1-01/EORTC 10011/BO16348B). BOOG 2003-02 (BIG 1-02/IBCSG 27-02). BOOG 2003-04 (GBG 29). BOOG 2004-02/TBP (GBG 26, BIG 3-05). BOOG 2005-01/CASA (IBCSG 32-05/BIG 1-05). BOOG 2005-03/MINDACT (EORTC 10041, BIG 3-04). BOOG 2006-03/SUPREMO (BIG 2-04). BOOG 2006-04/Adjuvant lapatinib study (BIG 2-06/EGF106708)

Fulvestrant ('Faslodex')--a new treatment option for patients progressing on prior endocrine therapy.

2002 ◽  
pp. 267-276 ◽  
Author(s):  
C Morris ◽  
A Wakeling
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Hormone Receptor Positive

Since its introduction more than 30 years ago, tamoxifen has been the most widely used endocrine therapy for the treatment of women with advanced breast cancer. More recently, a number of alternative endocrine treatments have been developed, including several selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and, most recently, fulvestrant ('Faslodex'). Fulvestrant is an estrogen receptor (ER) antagonist, which, unlike the SERMs, has no known agonist (estrogenic) effect and downregulates the ER protein. Tamoxifen is effective and well tolerated, although the non-steroidal AIs, anastrozole and letrozole, are more effective treatments for advanced disease than tamoxifen. Fulvestrant has recently gained US Food and Drug Administration approval for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. In two global phase III clinical trials fulvestrant was at least as effective and as equally well tolerated as anastrozole for the treatment of postmenopausal women with advanced and metastatic breast cancer. In a retrospective analysis of the combined data from these trials, mean duration of response was significantly greater for fulvestrant compared with anastrozole. These new hormonal treatments expand the choice of endocrine therapy for women with advanced breast cancer and offer new options for sequencing and combining treatments.

MONARCH 3: A randomized phase III study of anastrozole or letrozole plus abemaciclib, a CDK4/6 inhibitor, or placebo in first-line treatment of women with HR+, HER2-locoregionally recurrent or metastatic breast cancer (MBC).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. TPS624-TPS624
Author(s):  
Matthew P. Goetz ◽  
Masakazu Toi ◽  
Suzanne Klise ◽  
Martin Frenzel ◽  
Nawel Bourayou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Single Agent ◽  
Metastatic Breast ◽  
Adjuvant Endocrine Therapy ◽  
Phase Iii ◽  
Type I ◽  
First Line ◽  
Phase Iii Study

TPS624 Background: Abemaciclib (LY2835219), a cell cycle inhibitor of CDK4/CDK6, demonstrated a clinically manageable safety profile and single-agent anti-tumor activity in MBC; all tumor responses were observed in hormone receptor positive (HR+) disease (Tolaney SM, Rosen LS, Beeram M, et al. San Antonio Breast Cancer Symposium, 2014, Abstract P5-19-13). Non-steroidal aromatase inhibitors (NSAI, letrozole and anastrazole), approved in the first-line setting for postmenopausal women with HR+ MBC, are being evaluated in combination with abemaciclib for safety and tolerability in a phase Ib study (NCT02057133) and in the present study (NCT02246621) to assess clinical efficacy. Methods: MONARCH 3 is a randomized, double-blind, placebo-controlled, phase III study of abemaciclib + NSAI vs placebo + NSAI in locoregionally recurrent (not amenable to curative treatment) breast cancer or MBC, with no prior systemic therapy in this disease setting. Patients will be randomized 2:1, and stratified by nature of disease (visceral vs bone-only metastases vs other) and prior (neo)adjuvant endocrine therapy (aromatase inhibitor vs other vs none). Abemaciclib 150 mg or placebo will be given continuously PO every 12 hours until progression, along with anastrozole 1 mg or letrozole 2.5 mg once daily at the investigator’s discretion, and assessments will occur every 28 days. Postmenopausal women with HR+, HER2- disease, a disease-free interval > 12 mos after completion of (neo)adjuvant endocrine therapy, ECOG PS ≤ 1, adequate organ function, and measurable disease or nonmeasurable bone-only disease (RECIST v1.1) are eligible. The primary endpoint is progression-free survival (PFS); a key secondary endpoint is overall survival (OS). The study has 80% power to detect an increase in PFS of approximately 40% (hazard ratio = 0.714). Assuming a median PFS of 10 mos in the control arm, this corresponds to a 4-mo increase in the median PFS. PFS and OS will be hierarchically tested to maintain an overall type I error rate of 2.5%. Enrollment began November 2014; planned enrollment is 450 patients. Clinical trial information: NCT02246621.

scholarly journals Feasibility Trial of Letrozole in Combination With Bevacizumab in Patients With Metastatic Breast Cancer

2010 ◽  
Vol 28 (4) ◽  
pp. 628-633 ◽  
Author(s):  
Tiffany A. Traina ◽  
Hope S. Rugo ◽  
James F. Caravelli ◽  
Sujata Patil ◽  
Benjamin Yeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Stable Disease ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Feasibility Trial ◽  
Anti Vegf

Purpose Preclinical models suggest that the use of anti–vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor–positive metastatic breast cancer (MBC). Methods Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease. Results Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease ≥ 24 weeks was noted in 67%. Median PFS was 17.1 months. Conclusion Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).

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