Exemestane in metastatic breast cancer: Effective therapy after third-generation non-steroidal aromatase inhibitor failure

Steele, Nancy; Zekri, Jamal; Coleman, Robert E.; Leonard, R. C. F.; Dunn, Kathleen; Bowman, A.; Manifold, I; Kunkler, Ian; Purohit, O.P.; Cameron, David

doi:10.1016/j.breast.2005.08.032

Cited by 45 publications

(29 citation statements)

References 13 publications

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“…Therefore, further prospectively-designed analyses are required to ascertain whether fulvestrant offers any statistically significant benefits in patients with VM. However, as seen previously [9][10][11] there was also evidence for a lack of cross-resistance between exemestane and the non-steroidal AIs; it has been speculated that this may be due to the androgenic effects of exemestane [12]. These data, therefore, suggest that both fulvestrant and exemestane may be considered as suitable options for patients with VM who are eligible for further endocrine therapy, following non-steroidal AI failure.…”

Section: Discussionsupporting

confidence: 59%

“…With regard to exemestane, a previous Phase III trial evaluating this agent versus megestrol acetate found that CB rates were higher with exemestane (36.3%) than with megestrol acetate (30.0%) in patients with VM, although the difference was not significant [4]. In addition, a recent case series where exemestane was given following several prior therapies, including non-steroidal AIs, described a CB rate of 33.0% for patients with visceral involvement [10]. Despite the available data, it is difficult to compare the activity of different endocrine treatments between trials, due to differences in baseline patient characteristics, line of treatment or endpoint definitions.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, treatment options are limited when patients experience either progression or recurrence on non-steroidal AIs. There have been limited data to support the activity of both fulvestrant and exemestane in this setting, suggesting a lack of cross-resistance between these treatments and the nonsteroidal AIs [7][8][9][10][11]. Thus, there is an increasing need for alternative and effective treatments that can be used after non-steroidal AI failure, particularly in patients with VM, who are generally considered difficult to treat.…”

Section: Introductionmentioning

confidence: 99%

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Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial

Mauriac

Romieu²,

Bines

2008

Breast Cancer Res Treat

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Purpose Patients with visceral metastases (VM: lung and/or liver metastases) are generally regarded as being less responsive to hormonal therapy, and chemotherapy often becomes the default treatment. This paper reports a subgroup analysis from EFECT (The Evaluation of Faslodex versus Exemestane Clinical Trial) examining the efficacy of fulvestrant and exemestane in patients with or without VM. Methods EFECT is a randomised, doubleblind, multicentre, Phase III trial in postmenopausal women with advanced breast cancer progressing or recurring after prior non-steroidal aromatase inhibitor therapy. Results Overall, approximately 57% of patients in EFECT had visceral involvement. Fulvestrant and exemestane demonstrated clinical benefit in 29.1% and 27.2% of patients with VM, respectively. Median duration of response was 13.5 vs 10.8 months and median duration of clinical benefit was 9.9 vs 8.1 months, respectively. Conclusions These results encourage the use of endocrine agents such as fulvestrant in treating patients with advanced breast cancer and VM.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial

Mauriac

Romieu²,

Bines

2008

Breast Cancer Res Treat

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“…В целом, несмотря на многолетние исследования в области ГТ мРМЖ и создание стройного алгоритма последовательного назначения нескольких (как пра-вило, не менее 3) линий лечения, до последнего вре-мени не удавалось преодолеть определенное «плато» терапевтических возможностей: медиана выживаемо-сти без прогрессирования (ВБП) / времени до прогрес-сирования на любой схеме ГТ 1-й линии колебалась от 6 мес на тамоксифене до 12 мес по отдельным ис-следованиям ингибиторов ароматазы, а медиана ОВ составляла около 3 лет [13][14][15][16][17][18][19][20][21][22][23]. Ситуация стала не-сколько меняться с появлением эверолимуса (ингиби-тора mammalian target of rapamycin, mTOR), который улучшил результаты лечения мРМЖ, резистентного к нестероидным ингибиторам ароматазы.…”

Section: опухоли женской репродуктивной системы Tumors Of Female Reprunclassified

Palbociclib in Combination With Hormone Therapy for Luminal Her2-Negative Metastatic Breast Cancer: New Highly Effective Strategy of Drug Treatment

Артамонова¹

2017

Tumors of female reproductive system

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М а м м о л о г и я / M a m m o l o g y 3 ' 2 0 1 7 Том 13 / Vol. 13 1994-4098-2017-13-3-28-41 Palbociclib in combination with hormone therapy for luminal HER2-negative metastatic breast cancer: new highly effective strategy of drug treatment ОПУХОЛИ ЖЕНСКОЙ РЕПРОДУКТИВНОЙ СИСТЕМЫ TUMORS OF FEMALE REPRODUCTIVE SYSTEM E.V. Artamonova N.N. Blokhin National Medical Research Oncology Center, Ministry of Health of Russia; 23 Kashira Highway, Moscow 115478, Russia The review considers a new oral targeted drug palbociclib and its place in treatment of luminal (estrogen receptor-positive) HER2-metastatic breast cancer. The results of randomized clinical trials have shown that inclusion of palbociclib in various hormone therapy regimens for treatment of HER2-metastatic breast cancer with expression of estrogen receptors allows to significantly improve clinical outcomes and increase survival, objective response rate and its duration, as well as clinical benefit rate (CBR). Addition of palbociclib to letrozole in the 1 st line hormone therapy or to fulvestrant in patients with progression at/after previous endocrine therapy increased progression-free survival in all groups irrespective of clinical characteristics, tumor progression, or expression of molecular markers mediating development of hormone resistance.The main adverse events associated with palbociclib were neutropenia, leukopenia and thrombocytopenia, but overall hematological toxicity was manageable, and the therapy itself was safe. This strategy received a "breakthrough therapy designation" from the experts and combines proven effectiveness and satisfactory tolerability, allows to maintain high quality of life, and should be prescribed to patients with luminal HER2-metastatic breast cancer. Key words: metastatic breast cancer, hormone therapy, palbociclibРак молочной железы (РМЖ) остается ведущей онкологической патологией среди женского населе-ния России: в 2015 г. число вновь выявленных случаев достигло 66 621, а прирост заболеваемости за 10 лет составил 31,76 % [1, 2]. Как известно, прогноз при РМЖ определяется степенью распространенности процесса и принадлежностью опухоли к тому или ино-му молекулярному подтипу. К сожалению, результаты лечения даже самых ранних стадий относительно бла-гоприятного гормонозависимого РМЖ, на долю кото-рого приходится 60-65 %, далеки от идеала. Так, дли-тельное наблюдение за 46 138 больными ранним РМЖ с положительными рецепторами эстрогенов (ЭР+) показало, что проблема прогрессирования после окон-чания стандартной 5-летней адъювантной гормоноте-рапии (ГТ) является весьма существенной. При

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“…Upon progression of metastatic disease following treatment with NSAIs, exemestane may be effective as sequential hormone therapy (Lønning et al 2000, Bertelli & Paridaens 2006, Steele et al 2006, Lønning 2009, Kim et al 2012. Several trials have found that breast cancer patients who have become resistant to NSAIs may experience benefit from SAIs (Table 2; Thürlimann et al 1997, Lønning et al 2000, Bertelli et al 2005, Iaffaioli et al 2005, Gennatas et al 2006, Mayordomo et al 2006, Steele et al 2006, Carlini et al 2007, Chin et al 2007, Mauriac et al 2009). On average, 25-30% of patients in these cross-over studies experienced objective response or stable disease for 6 months or more.…”

Section: In the Evaluation Of Faslodex Vs Exemestane Clinicalmentioning

confidence: 99%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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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. Furthermore, this AI has been studied in the neoadjuvant setting as presurgical treatment, and even as chemoprevention in high-risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such as endometrial changes and thromboembolic disease but may also cause some inconvenient side effects itself. Additionally, there is a lack of total crossresistance between exemestane and nonsteroidal AIs as far as their anti-tumoral efficacy is concerned; moreover the two classes of AIs display a nontotal overlapping toxicity profile. Taking together, exemestane can be considered as a useful treatment option at all stages of breast cancer.

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Exemestane in metastatic breast cancer: Effective therapy after third-generation non-steroidal aromatase inhibitor failure

Cited by 45 publications

References 13 publications

Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial

Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial

Palbociclib in Combination With Hormone Therapy for Luminal Her2-Negative Metastatic Breast Cancer: New Highly Effective Strategy of Drug Treatment

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

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