A comparative study of exemestane versus anastrozole in patients with postmenopausal breast cancer with visceral metastases (original) (raw)
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Cancer, 2012
BACKGROUND: Several aromatase inhibitor studies have reported variations in the inhibitory potency of these agents that could lead to differences in clinical outcomes. In the current study, the authors formally evaluated the activity of anastrozole and exemestane in postmenopausal women with hormone-responsive, advanced breast cancer. METH-ODS: Postmenopausal women who had measurable disease according to Response Evaluation Criteria in Solid Tumors and had not received previous endocrine therapy for advanced breast cancer were randomized to receive either oral exemestane 25 mg daily or oral anastrozole 1 mg daily until they had disease progression. The primary endpoint was the objective response rate (ORR), and secondary endpoints included the clinical benefit rate (CBR), time to progression (TTP), overall survival, and safety. Crossover to the other aromatase inhibitor was permitted at the time of disease progression; ORR, CBR, and TTP after second-line treatment also were explored. RESULTS: In total, 103 patients were enrolled. The median patient age was 71.6 years, 52.4% of patients had visceral disease, and 75.8% of patients had 2 disease sites. Half of the patients had received previous tamoxifen, and 60% had received previous chemotherapy. The efficacy observed in the exemestane and anastrozole groups was an ORR of 36.2% and 46%, respectively; a CBR of 59.6% and 68%, respectively, and a TTP of 6.1 months and 12.1 months, respectively. At progression, 28 patients crossed over to the other aromatase inhibitor, including 16 patients who switched to exemestane (CBR, 43.7%; TTP, 4.4 months) and 12 patients who switched to anastrozole (CBR, 8.3%; TTP, 2 months). Both drugs were generally well tolerated, and no study drug-related serious adverse events were reported. CONCLUSIONS: In this phase 2 randomized trial, no significant differences in clinical activity were observed in favor of exemestane to justify a superiority phase 3 trial design in the first-line setting. Cancer 2012;118:241-7
Breast Cancer Research and Treatment, 2013
The aromatase inhibitors exemestane and anastrozole are approved in Japan for first-line treatment of postmenopausal patients with advanced, hormone-receptor-positive breast cancer. This phase 3, randomized, double-blind study directly compared time to progression (TTP) for exemestane and anastrozole therapy in this patient population. Eligible patients were randomized to receive exemestane 25 mg or anastrozole 1 mg, each once daily. The primary endpoint was TTP based on assessment by an expert radiologic images review committee (ERIRC). Secondary endpoints included investigator-assessed TTP, time to treatment failure, overall survival, objective response rate, clinical benefit rate, and safety. A total 298 patients were randomized to receive exemestane (n = 149; mean age 63.4 years) or anastrozole (n = 149; mean age Presented in part at the 34th San Antonio Breast
The Lancet Oncology, 2013
Background The optimum endocrine treatment for postmenopausal women with advanced hormone-receptorpositive breast cancer that has progressed on non-steroidal aromatase inhibitors (NSAIs) is unclear. The aim of the SoFEA trial was to assess a maximum double endocrine targeting approach with the steroidal anti-oestrogen fulvestrant in combination with continued oestrogen deprivation. Methods In a composite, multicentre, phase 3 randomised controlled trial done in the UK and South Korea, postmenopausal women with hormone-receptor-positive breast cancer (oestrogen receptor [ER] positive, progesterone receptor [PR] positive, or both) were eligible if they had relapsed or progressed with locally advanced or metastatic disease on an NSAI (given as adjuvant for at least 12 months or as fi rst-line treatment for at least 6 months). Additionally, patients had to have adequate organ function and a WHO performance status of 0-2. Participants were randomly assigned (1:1:1) to receive fulvestrant (500 g intramuscular injection on day 1, followed by 250 mg doses on days 15 and 29, and then every 28 days) plus daily oral anastrozole (1 mg); fulvestrant plus anastrozole-matched placebo; or daily oral exemestane (25 mg). Randomisation was done with computer-generated permuted blocks, and stratifi cation was by centre and previous use of an NSAI as adjuvant treatment or for locally advanced or metastatic disease. Participants and investigators were aware of assignment to fulvestrant or exemestane, but not of assignment to anastrozole or placebo. The primary endpoint was progression-free survival (PFS). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, numbers NCT00253422 (UK) and NCT00944918 (South Korea).
Breast Cancer Research and Treatment, 2010
To undertake a systematic review of three firstline treatments (letrozole, anastrozole and exemestane) for hormone sensitive advanced or metastatic breast cancer (MBC) in post-menopausal women. We searched six databases from inception up to January 2009 for relevant trials regardless of language or publication status. Randomised controlled clinical trials assessing the safety and efficacy of first-line AIs for post-menopausal women with hormone receptor-positive (HR?, i.e. ER? and/or PgR?) with or without ErbB2 (HER2)-positive MBC, who have not received prior therapy for advanced or metastatic disease were included. Where meta-analysis using direct or indirect comparisons was considered unsuitable for some or all of the data, we employed a narrative synthesis method. Four studies (25 papers) met the inclusion criteria. From the available evidence, it was possible to directly compare the three AIs with tamoxifen. In addition, by using a network meta-analysis it was possible to compare the three AIs with each other. Based on direct evidence, letrozole seemed to be significantly better than tamoxifen in terms of time-toprogression (TTP) (HR = 0.70 (95% CI: 0.60, 0.82)), objective response rate (RR = 0.65 (95% CI: 0.52, 0.82)) and quality-adjusted time without symptoms or toxicity (Q-Twist difference = 1.5; P \ 0.001). Exemestane seemed significantly superior to tamoxifen in terms of objective response rate (RR = 0.68 (95% CI: 0.53, 0.89)). Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR = 1.42 (95% CI: 1.15, NR)), but not in the other (HR = 1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen. Tamoxifen was associated with significantly more serious adverse events in comparison with exemestane (OR = 0.61 (95% CI: 0.38, 0.97)); while exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR = 2.33 (95% CI: 1.07, 5.11)). Anastrozole was associated with significantly more total adverse events (OR = 1.04 (95% CI: 1.00, 1.09)) and hot flushes (OR = 1.39 (95% CI: 1.03, 1.89)) in comparison with tamoxifen in one trial; however, the other trial showed no significant differences in adverse events between anastrozole and tamoxifen. The indirect comparison of AIs with each other in women with postmenopausal, hormone sensitive advanced or MBC showed that letrozole and exemestane were better in terms of objective response rate than anastrozole; while the more clinically relevant outcomes overall survival (OS) and progression-free survival (PFS) showed no significant differences between AIs. OS and PFS showed no significant differences between AIs and hence based on these results a class effect for all AIs is possible. However, these results are based on indirect comparisons and a network analysis for which the basic assumptions of homogeneity, similarity and consistency were not fulfilled. Therefore, despite the fact that these are the best available data, the results need to be interpreted with appropriate caution. Head-to-head comparisons between letrozole, anastrozole and exemestane in the first-line MBC setting are warranted.
Tumori Journal, 2006
Aims and background:The understanding of hormonal therapies in in the study. All patients had received two prior hormonal mapostmenopausal women with metastatic breast cancer has adnipulations and had measurable or assessable disease. All vanced greatly in the past several decades. With the introduction adverse events were monitored. of orally active, potent and selective third-generation aromatase Results: Objective tumor response was achieved in 12 (20%) inhibitors (anastrozole, letrozole and exemestane), approaches patients (95% CI, 9.6-30.4). The overall clinical benefit was to the treatment of hormone-sensitive advanced breast cancer 38.3% (95% CI, 21.2-49.3), and the median duration of objectiare undergoing reevaluation. For treatment of advanced or meta-ve tumor response was 20 months (range, 9-26). The median static disease that has progressed on tamoxifen, all three agents time to death was 17.4 months (95% CI, 16.14-18.66). are active. The purpose of the study was to assess the antitumor Conclusions: Exemestane represents an active and well-toleraefficacy and tolerance of exemestane administered as third-line ted treatment option in pretreated patients with advanced hormonal therapy to postmenopausal women with metastatic breast cancer who have received standard first-and secondbreast cancer refractory to letrozole and anastrozole. line hormonal therapies. By extending the sequence of hor-Study design: Sixty postmenopausal women with stage IV hormonal therapy, disease progression and the need for chemone receptor-positive carcinoma of the breast were enrolled motherapy may be significantly delayed.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2000
To evaluate the antitumor activity and toxicity of a new steroidal aromatase inactivator, exemestane, in postmenopausal women with metastatic breast cancer who had progressive disease (PD) after treatment with a nonsteroidal aromatase inhibitor. In this phase II trial, eligible patients were treated with exemestane 25 mg daily (n = 241) followed, at the time PD was determined, by exemestane 100 mg daily (n = 58). On the basis of the intent-to-treat analysis by independent review, exemestane 25 mg produced objective responses in 6.6% of patients (95% confidence interval [CI], 3.8% to 10.6%) and overall success (complete response + partial response + no change for 24 weeks or longer) in 24.3% (95% CI, 19.0% to 30.2%). The median durations of objective response and overall success were 58.4 weeks (95% CI, 49.7 to 71.1 weeks) and 37.0 weeks (95% CI, 35.0 to 39.4 weeks), respectively. Increasing the dose of exemestane to 100 mg upon the development of PD produced one partial response (1....
Aromatase inhibitors in the breast cancer clinic: focus on exemestane
Endocrine Related Cancer, 2014
Breast cancer is the most prevalent type of cancer in women and responsible for significant female cancer-related mortality worldwide. In the Western world, over 80% of breast cancers are hormone-receptor positive for which endocrine therapy is administered. The main anti-estrogen treatments in use consist of selective estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review, the focus will lie on exemestane, its clinical use, and its side-effect profile. Exemestane is the only third-generation steroidal AI. Its efficacy as a first-line treatment in metastatic breast cancer has been demonstrated. Therefore, exemestane could be considered a valid first-line therapeutic option, but it also can be used in second-line or further situations. Exemestane is mostly used as part of sequential adjuvant treatment following tamoxifen, but in this setting it is also active in monotherapy. Furt...
Breast Cancer Research and Treatment, 2003
Tumors that have spread to the liver or lungs (visceral metastases) are associated with a worse prognosis than tumors in soft tissue and bone only. Here we review available efficacy data to address whether or not anastrozole, a non-steroidal aromatase inhibitor (AI), is effective in postmenopausal patients with advanced breast cancer (ABC) and visceral metastases. We include data from Phase III clinical trials, comparing clinical benefit (CB) with anastrozole versus tamoxifen as a first-line treatment, and versus megestrol acetate (MA) or fulvestrant as a second-line therapy. Patients in these trials had adequate organ function and the volume of disease had to be minimal or moderate for them to be eligible for inclusion. First-line treatment of patients with or without visceral metastases in the overall population resulted in CB rates of 49.5 and 62.3%, respectively, for anastrozole and 46.9 and 55.9%, respectively, for tamoxifen. In patients with confirmed hormone receptor (HR)-positive tumors, the CB rate was 51.9 and 65.7%, respectively, for anastrozole and 41.6 and 58.7%, respectively, for tamoxifen. In patients with or without visceral metastases, second-line treatment with anastrozole resulted in a CB rate of 31.4 and 51.8%, respectively, compared with 31.9 and 47.1%, respectively, for those treated with MA. Patients in the overall population with and without visceral metastases treated with anastrozole obtained a CB rate of 37.4 and 43.8%, respectively, while those treated with fulvestrant obtained a CB rate of 38.2 and 47.6%, respectively. In patients with confirmed HR-positive tumors, CB was seen in 37.6 and 41.5%, respectively, of patients treated with anastrozole and in 37.3 and 47.0%, respectively, of patients treated with fulvestrant. The results reveal anastrozole to be an effective and valuable first-and second-line therapy in postmenopausal women with ABC and visceral metastases, showing similar CB to other endocrine therapies.
Breast Diseases: A Year Book Quarterly, 2006
Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and 424 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6 -36.8%). An additional 46 patients had long-term (424 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2 -81.4). Median time to progression (TTP) was 11 months (95% CI: 10 -12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted X6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy.
Aromatase Inhibitors in advanced breast cancer
2010
A number of potent and selective non-steroidal aromatase inhibitors are now available for treatment of advanced breast cancer in postmenopausal women, of which anastrozole and letrozole, in particular, represent a significant advantage over the earlier agents in terms of both efficacy and tolerability. These agents are rapidly becoming established as the second-line therapy of choice in postmenopausal women with advanced disease, progressing on tamoxifen, and data on their efficacy as first-line treatment compared with tamoxifen will be available in the near future. Exemestane, a new, steroidal aromatase inhibitor which potentially lacks cross-resistance with non-steroidal agents is still in clinical development. The full potential of the new-generation aromatase inhibitors in the treatment of breast cancer is currently being investigated in a large program of clinical trials evaluating their use Endocrine-Related Cancer (1999) 6 219-225 as adjuvant treatment following surgery in postmenopausal patients with early disease.