Everolimus plus endocrine therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A clinical trial

Melanie Royce, Thomas Bachelot, Cristian Villanueva, Mustafa Özgüroglu, Sergio J. Azevedo, Felipe Melo Cruz, Marc Debled, Roberto Hegg, Tatsuya Toyama, Carla Falkson, Joon Jeong, Vichien Srimuninnimit, William J. Gradishar, Christina Arce, Antonia Ridolfi, Chinjune Lin, Fatima Cardoso

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

IMPORTANCE Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer. OBJECTIVE To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer. DESIGN, SETTING, AND PARTICIPANTS In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014. A median follow-up of 29.5 months had been achieved by the data cutoff date (December 17, 2016). INTERVENTIONS Patients received first-line treatment with everolimus, 10mg/d, plus letrozole, 2.5mg/d. Second-line treatment with everolimus, 10mg/d, plus exemestane, 25 mg/d, was offered at the investigator's discretion upon initial disease progression. MAIN OUTCOMES AND MEASURES The primary end pointwas investigator-assessed progression-free survival in the first-line setting per Response Evaluation Criteria in Solid Tumors, version 1.0. Safety was assessed in patients who received at least 1 dose of study medication and at least 1 postbaseline safety assessment. RESULTS A total of 202 women treated in the first-line setting had a median age of 64.0 years (interquartile range, 58.0-70.0 years) with metastatic (194 [96.0%]) or locally advanced (8 [4.0%]) breast cancer. Median progression-free survival was 22.0 months (95%CI, 18.1-25.1 months) with everolimus and letrozole. Median overall survival was not reached; 24-month estimated overall survival rate was 78.7%(95%CI, 72.1%-83.9%). Fifty patients started second-line treatment; median progression-free survival was 3.7 months (95%CI, 1.9-7.4 months). No new safety signals were observed. In the first-line setting, the most common all-grade adverse event was stomatitis (139 [68.8%]); the most common grade 3 to 4 adverse event was anemia (21 [10.4%]). In the second-line setting, the most common adverse events were stomatitis and decreased weight (10 [20.0%] each); the most common grade 3 to 4 adverse event was hypertension (5 [10.0%]). There were 50 (24.8%) deaths overall during the study; 40 were due to study indication (breast cancer). CONCLUSIONS AND RELEVANCE The results of this trial add to the existing body of evidence suggesting that everolimus plus endocrine therapy is a good first-line treatment option for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.

Original languageEnglish
Pages (from-to)977-984
Number of pages8
JournalJAMA Oncology
Volume4
Issue number7
DOIs
Publication statusPublished - 2018 Jul

Fingerprint

Estrogen Receptors
Clinical Trials
Breast Neoplasms
letrozole
Disease-Free Survival
Stomatitis
exemestane
Therapeutics
Safety
Research Personnel
human ERBB2 protein
Everolimus
Mouth Neoplasms
Sirolimus
Disease Progression
Anemia
Survival Rate
Hypertension
Weights and Measures
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Royce, Melanie ; Bachelot, Thomas ; Villanueva, Cristian ; Özgüroglu, Mustafa ; Azevedo, Sergio J. ; Cruz, Felipe Melo ; Debled, Marc ; Hegg, Roberto ; Toyama, Tatsuya ; Falkson, Carla ; Jeong, Joon ; Srimuninnimit, Vichien ; Gradishar, William J. ; Arce, Christina ; Ridolfi, Antonia ; Lin, Chinjune ; Cardoso, Fatima. / Everolimus plus endocrine therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer : A clinical trial. In: JAMA Oncology. 2018 ; Vol. 4, No. 7. pp. 977-984.
@article{61b30c234b1f45e69b20fd39439795eb,
title = "Everolimus plus endocrine therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A clinical trial",
abstract = "IMPORTANCE Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer. OBJECTIVE To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer. DESIGN, SETTING, AND PARTICIPANTS In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014. A median follow-up of 29.5 months had been achieved by the data cutoff date (December 17, 2016). INTERVENTIONS Patients received first-line treatment with everolimus, 10mg/d, plus letrozole, 2.5mg/d. Second-line treatment with everolimus, 10mg/d, plus exemestane, 25 mg/d, was offered at the investigator's discretion upon initial disease progression. MAIN OUTCOMES AND MEASURES The primary end pointwas investigator-assessed progression-free survival in the first-line setting per Response Evaluation Criteria in Solid Tumors, version 1.0. Safety was assessed in patients who received at least 1 dose of study medication and at least 1 postbaseline safety assessment. RESULTS A total of 202 women treated in the first-line setting had a median age of 64.0 years (interquartile range, 58.0-70.0 years) with metastatic (194 [96.0{\%}]) or locally advanced (8 [4.0{\%}]) breast cancer. Median progression-free survival was 22.0 months (95{\%}CI, 18.1-25.1 months) with everolimus and letrozole. Median overall survival was not reached; 24-month estimated overall survival rate was 78.7{\%}(95{\%}CI, 72.1{\%}-83.9{\%}). Fifty patients started second-line treatment; median progression-free survival was 3.7 months (95{\%}CI, 1.9-7.4 months). No new safety signals were observed. In the first-line setting, the most common all-grade adverse event was stomatitis (139 [68.8{\%}]); the most common grade 3 to 4 adverse event was anemia (21 [10.4{\%}]). In the second-line setting, the most common adverse events were stomatitis and decreased weight (10 [20.0{\%}] each); the most common grade 3 to 4 adverse event was hypertension (5 [10.0{\%}]). There were 50 (24.8{\%}) deaths overall during the study; 40 were due to study indication (breast cancer). CONCLUSIONS AND RELEVANCE The results of this trial add to the existing body of evidence suggesting that everolimus plus endocrine therapy is a good first-line treatment option for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.",
author = "Melanie Royce and Thomas Bachelot and Cristian Villanueva and Mustafa {\"O}zg{\"u}roglu and Azevedo, {Sergio J.} and Cruz, {Felipe Melo} and Marc Debled and Roberto Hegg and Tatsuya Toyama and Carla Falkson and Joon Jeong and Vichien Srimuninnimit and Gradishar, {William J.} and Christina Arce and Antonia Ridolfi and Chinjune Lin and Fatima Cardoso",
year = "2018",
month = "7",
doi = "10.1001/jamaoncol.2018.0060",
language = "English",
volume = "4",
pages = "977--984",
journal = "JAMA oncology",
issn = "2374-2437",
publisher = "American Medical Association",
number = "7",

}

Royce, M, Bachelot, T, Villanueva, C, Özgüroglu, M, Azevedo, SJ, Cruz, FM, Debled, M, Hegg, R, Toyama, T, Falkson, C, Jeong, J, Srimuninnimit, V, Gradishar, WJ, Arce, C, Ridolfi, A, Lin, C & Cardoso, F 2018, 'Everolimus plus endocrine therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A clinical trial', JAMA Oncology, vol. 4, no. 7, pp. 977-984. https://doi.org/10.1001/jamaoncol.2018.0060

Everolimus plus endocrine therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer : A clinical trial. / Royce, Melanie; Bachelot, Thomas; Villanueva, Cristian; Özgüroglu, Mustafa; Azevedo, Sergio J.; Cruz, Felipe Melo; Debled, Marc; Hegg, Roberto; Toyama, Tatsuya; Falkson, Carla; Jeong, Joon; Srimuninnimit, Vichien; Gradishar, William J.; Arce, Christina; Ridolfi, Antonia; Lin, Chinjune; Cardoso, Fatima.

In: JAMA Oncology, Vol. 4, No. 7, 07.2018, p. 977-984.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Everolimus plus endocrine therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

T2 - A clinical trial

AU - Royce, Melanie

AU - Bachelot, Thomas

AU - Villanueva, Cristian

AU - Özgüroglu, Mustafa

AU - Azevedo, Sergio J.

AU - Cruz, Felipe Melo

AU - Debled, Marc

AU - Hegg, Roberto

AU - Toyama, Tatsuya

AU - Falkson, Carla

AU - Jeong, Joon

AU - Srimuninnimit, Vichien

AU - Gradishar, William J.

AU - Arce, Christina

AU - Ridolfi, Antonia

AU - Lin, Chinjune

AU - Cardoso, Fatima

PY - 2018/7

Y1 - 2018/7

N2 - IMPORTANCE Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer. OBJECTIVE To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer. DESIGN, SETTING, AND PARTICIPANTS In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014. A median follow-up of 29.5 months had been achieved by the data cutoff date (December 17, 2016). INTERVENTIONS Patients received first-line treatment with everolimus, 10mg/d, plus letrozole, 2.5mg/d. Second-line treatment with everolimus, 10mg/d, plus exemestane, 25 mg/d, was offered at the investigator's discretion upon initial disease progression. MAIN OUTCOMES AND MEASURES The primary end pointwas investigator-assessed progression-free survival in the first-line setting per Response Evaluation Criteria in Solid Tumors, version 1.0. Safety was assessed in patients who received at least 1 dose of study medication and at least 1 postbaseline safety assessment. RESULTS A total of 202 women treated in the first-line setting had a median age of 64.0 years (interquartile range, 58.0-70.0 years) with metastatic (194 [96.0%]) or locally advanced (8 [4.0%]) breast cancer. Median progression-free survival was 22.0 months (95%CI, 18.1-25.1 months) with everolimus and letrozole. Median overall survival was not reached; 24-month estimated overall survival rate was 78.7%(95%CI, 72.1%-83.9%). Fifty patients started second-line treatment; median progression-free survival was 3.7 months (95%CI, 1.9-7.4 months). No new safety signals were observed. In the first-line setting, the most common all-grade adverse event was stomatitis (139 [68.8%]); the most common grade 3 to 4 adverse event was anemia (21 [10.4%]). In the second-line setting, the most common adverse events were stomatitis and decreased weight (10 [20.0%] each); the most common grade 3 to 4 adverse event was hypertension (5 [10.0%]). There were 50 (24.8%) deaths overall during the study; 40 were due to study indication (breast cancer). CONCLUSIONS AND RELEVANCE The results of this trial add to the existing body of evidence suggesting that everolimus plus endocrine therapy is a good first-line treatment option for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.

AB - IMPORTANCE Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer. OBJECTIVE To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer. DESIGN, SETTING, AND PARTICIPANTS In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014. A median follow-up of 29.5 months had been achieved by the data cutoff date (December 17, 2016). INTERVENTIONS Patients received first-line treatment with everolimus, 10mg/d, plus letrozole, 2.5mg/d. Second-line treatment with everolimus, 10mg/d, plus exemestane, 25 mg/d, was offered at the investigator's discretion upon initial disease progression. MAIN OUTCOMES AND MEASURES The primary end pointwas investigator-assessed progression-free survival in the first-line setting per Response Evaluation Criteria in Solid Tumors, version 1.0. Safety was assessed in patients who received at least 1 dose of study medication and at least 1 postbaseline safety assessment. RESULTS A total of 202 women treated in the first-line setting had a median age of 64.0 years (interquartile range, 58.0-70.0 years) with metastatic (194 [96.0%]) or locally advanced (8 [4.0%]) breast cancer. Median progression-free survival was 22.0 months (95%CI, 18.1-25.1 months) with everolimus and letrozole. Median overall survival was not reached; 24-month estimated overall survival rate was 78.7%(95%CI, 72.1%-83.9%). Fifty patients started second-line treatment; median progression-free survival was 3.7 months (95%CI, 1.9-7.4 months). No new safety signals were observed. In the first-line setting, the most common all-grade adverse event was stomatitis (139 [68.8%]); the most common grade 3 to 4 adverse event was anemia (21 [10.4%]). In the second-line setting, the most common adverse events were stomatitis and decreased weight (10 [20.0%] each); the most common grade 3 to 4 adverse event was hypertension (5 [10.0%]). There were 50 (24.8%) deaths overall during the study; 40 were due to study indication (breast cancer). CONCLUSIONS AND RELEVANCE The results of this trial add to the existing body of evidence suggesting that everolimus plus endocrine therapy is a good first-line treatment option for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=85050538909&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050538909&partnerID=8YFLogxK

U2 - 10.1001/jamaoncol.2018.0060

DO - 10.1001/jamaoncol.2018.0060

M3 - Article

C2 - 29566104

AN - SCOPUS:85050538909

VL - 4

SP - 977

EP - 984

JO - JAMA oncology

JF - JAMA oncology

SN - 2374-2437

IS - 7

ER -