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Everolimus overcomes hormonal resistance in ER-positive breast cancer
The addition of everolimus to exemestane more than doubled progression-free survival in women with advanced breast cancer who became resistant to hormonal therapy.

A preplanned interim analysis of the phase III BOLERO- 2 trial in women with advanced hormone-resistant, estrogen receptor– positive (ER+) breast cancer showed that everolimus (Afinitor) combined with the aromatase inhibitor exemestane increased progression-free survival (PFS), by local assessment, from a median of 2.8 months with exemestane alone to 6.9 months—a 57% risk reduction (hazard ratio [HR], 0.43; P = 1.4 × 10–15). The results were presented at the recent 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden.1

Based on central assessment, the everolimus-exemestane combination produced a 64% reduction in the risk of progression or death (10.6 months vs 4.1 months; HR = 0.36; P = 3.3 × 10–15), according to lead investigator José Baselga, MD, PhD, of the Massachusetts General Hospital Cancer Center in Boston.

The researchers evaluated everolimus because the mammalian target of rapamycin (mTOR) pathway is activated in hormone therapy–resistant advanced breast cancer. Phase II everolimus trials have suggested that the mTORC1 inhibitor could reverse resistance to endocrine therapy.2

The group enrolled 724 postmenopausal women (median age, 62 years) with advanced ER+, human epidermal growth factor receptor 2–negative (HER2–) breast cancer who were refractory to letrozole or anastrozole. Previous treatment also included chemotherapy for metastatic disease in roughly 68% of the patients, tamoxifen in 48%, and fulvestrant (Faslodex) in about 16%. The patients were randomized to treatment with everolimus 10 mg/d or placebo, with both arms receiving exemestane 25 mg/d. Treatment was continued until disease progression or unacceptable toxicity occurred. The primary endpoint was PFS, as assessed by the investigators; secondary endpoints included survival, response rate, and safety. The preplanned interim analysis was performed and reviewed by an independent data monitoring committee after observing 359 PFS events.

* For a PDF of the full article, click in the link to the left of this introduction.

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The addition of everolimus to exemestane more than doubled progression-free survival in women with advanced breast cancer who became resistant to hormonal therapy.
The addition of everolimus to exemestane more than doubled progression-free survival in women with advanced breast cancer who became resistant to hormonal therapy.

A preplanned interim analysis of the phase III BOLERO- 2 trial in women with advanced hormone-resistant, estrogen receptor– positive (ER+) breast cancer showed that everolimus (Afinitor) combined with the aromatase inhibitor exemestane increased progression-free survival (PFS), by local assessment, from a median of 2.8 months with exemestane alone to 6.9 months—a 57% risk reduction (hazard ratio [HR], 0.43; P = 1.4 × 10–15). The results were presented at the recent 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden.1

Based on central assessment, the everolimus-exemestane combination produced a 64% reduction in the risk of progression or death (10.6 months vs 4.1 months; HR = 0.36; P = 3.3 × 10–15), according to lead investigator José Baselga, MD, PhD, of the Massachusetts General Hospital Cancer Center in Boston.

The researchers evaluated everolimus because the mammalian target of rapamycin (mTOR) pathway is activated in hormone therapy–resistant advanced breast cancer. Phase II everolimus trials have suggested that the mTORC1 inhibitor could reverse resistance to endocrine therapy.2

The group enrolled 724 postmenopausal women (median age, 62 years) with advanced ER+, human epidermal growth factor receptor 2–negative (HER2–) breast cancer who were refractory to letrozole or anastrozole. Previous treatment also included chemotherapy for metastatic disease in roughly 68% of the patients, tamoxifen in 48%, and fulvestrant (Faslodex) in about 16%. The patients were randomized to treatment with everolimus 10 mg/d or placebo, with both arms receiving exemestane 25 mg/d. Treatment was continued until disease progression or unacceptable toxicity occurred. The primary endpoint was PFS, as assessed by the investigators; secondary endpoints included survival, response rate, and safety. The preplanned interim analysis was performed and reviewed by an independent data monitoring committee after observing 359 PFS events.

* For a PDF of the full article, click in the link to the left of this introduction.

A preplanned interim analysis of the phase III BOLERO- 2 trial in women with advanced hormone-resistant, estrogen receptor– positive (ER+) breast cancer showed that everolimus (Afinitor) combined with the aromatase inhibitor exemestane increased progression-free survival (PFS), by local assessment, from a median of 2.8 months with exemestane alone to 6.9 months—a 57% risk reduction (hazard ratio [HR], 0.43; P = 1.4 × 10–15). The results were presented at the recent 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden.1

Based on central assessment, the everolimus-exemestane combination produced a 64% reduction in the risk of progression or death (10.6 months vs 4.1 months; HR = 0.36; P = 3.3 × 10–15), according to lead investigator José Baselga, MD, PhD, of the Massachusetts General Hospital Cancer Center in Boston.

The researchers evaluated everolimus because the mammalian target of rapamycin (mTOR) pathway is activated in hormone therapy–resistant advanced breast cancer. Phase II everolimus trials have suggested that the mTORC1 inhibitor could reverse resistance to endocrine therapy.2

The group enrolled 724 postmenopausal women (median age, 62 years) with advanced ER+, human epidermal growth factor receptor 2–negative (HER2–) breast cancer who were refractory to letrozole or anastrozole. Previous treatment also included chemotherapy for metastatic disease in roughly 68% of the patients, tamoxifen in 48%, and fulvestrant (Faslodex) in about 16%. The patients were randomized to treatment with everolimus 10 mg/d or placebo, with both arms receiving exemestane 25 mg/d. Treatment was continued until disease progression or unacceptable toxicity occurred. The primary endpoint was PFS, as assessed by the investigators; secondary endpoints included survival, response rate, and safety. The preplanned interim analysis was performed and reviewed by an independent data monitoring committee after observing 359 PFS events.

* For a PDF of the full article, click in the link to the left of this introduction.

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Everolimus overcomes hormonal resistance in ER-positive breast cancer
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Everolimus overcomes hormonal resistance in ER-positive breast cancer
Legacy Keywords
everolimus, exemestane, ER-positive, breast cancer, survival
Legacy Keywords
everolimus, exemestane, ER-positive, breast cancer, survival
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