Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer in PALOMA-3

M. Cristofanilli, A. DeMichele, C. Giorgetti, N.C. Turner, D.J. Slamon, S.-A. Im, N. Masuda, S. Verma, S. Loi, M. Colleoni, K.P. Theall, X. Huang, Y. Liu, C.H. Bartlett

Research output: Contribution to journalArticle

Abstract

Background: The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit. Methods: Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174). Baseline characteristics, mutation status and HR expression levels were compared in patients with and without prolonged benefit (treatment duration ≥18 months). Results: By August 2016, 100 patients (29%) on palbociclib-fulvestrant and 26 (15%) on placebo-fulvestrant demonstrated prolonged benefit, with long-term responders in both arms sharing common clinical characteristics. They usually had less disease burden at baseline versus those treated
Original languageEnglish
Pages (from-to)21-31
Number of pages11
JournalEuropean journal of cancer
Volume104
DOIs
Publication statusPublished - 2018

Fingerprint

Epidermal Growth Factor Receptor
Hormones
Breast Neoplasms
Placebos
Appointments and Schedules
palbociclib
fulvestrant
Mutation
Therapeutics

Keywords

  • Advanced breast cancer
  • Fulvestrant
  • HR+/HER2–
  • Long-term response
  • Palbociclib
  • estrogen receptor
  • fulvestrant
  • palbociclib
  • placebo
  • progesterone receptor
  • adult
  • aged
  • Article
  • cancer hormone therapy
  • cancer patient
  • clinical outcome
  • controlled study
  • disease burden
  • esr1 gene
  • female
  • gene mutation
  • human
  • major clinical study
  • metastatic breast cancer
  • multicenter study
  • mutation rate
  • pik3ca gene
  • postmenopause
  • premenopause
  • priority journal
  • randomized controlled trial
  • treatment response
  • tumor gene

Cite this

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer in PALOMA-3. / Cristofanilli, M.; DeMichele, A.; Giorgetti, C.; Turner, N.C.; Slamon, D.J.; Im, S.-A.; Masuda, N.; Verma, S.; Loi, S.; Colleoni, M.; Theall, K.P.; Huang, X.; Liu, Y.; Bartlett, C.H.

In: European journal of cancer, Vol. 104, 2018, p. 21-31.

Research output: Contribution to journalArticle

Cristofanilli, M. ; DeMichele, A. ; Giorgetti, C. ; Turner, N.C. ; Slamon, D.J. ; Im, S.-A. ; Masuda, N. ; Verma, S. ; Loi, S. ; Colleoni, M. ; Theall, K.P. ; Huang, X. ; Liu, Y. ; Bartlett, C.H. / Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer in PALOMA-3. In: European journal of cancer. 2018 ; Vol. 104. pp. 21-31.
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title = "Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer in PALOMA-3",
abstract = "Background: The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit. Methods: Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174). Baseline characteristics, mutation status and HR expression levels were compared in patients with and without prolonged benefit (treatment duration ≥18 months). Results: By August 2016, 100 patients (29{\%}) on palbociclib-fulvestrant and 26 (15{\%}) on placebo-fulvestrant demonstrated prolonged benefit, with long-term responders in both arms sharing common clinical characteristics. They usually had less disease burden at baseline versus those treated",
keywords = "Advanced breast cancer, Fulvestrant, HR+/HER2–, Long-term response, Palbociclib, estrogen receptor, fulvestrant, palbociclib, placebo, progesterone receptor, adult, aged, Article, cancer hormone therapy, cancer patient, clinical outcome, controlled study, disease burden, esr1 gene, female, gene mutation, human, major clinical study, metastatic breast cancer, multicenter study, mutation rate, pik3ca gene, postmenopause, premenopause, priority journal, randomized controlled trial, treatment response, tumor gene",
author = "M. Cristofanilli and A. DeMichele and C. Giorgetti and N.C. Turner and D.J. Slamon and S.-A. Im and N. Masuda and S. Verma and S. Loi and M. Colleoni and K.P. Theall and X. Huang and Y. Liu and C.H. Bartlett",
note = "Cited By :1 Export Date: 6 February 2019 CODEN: EJCAE Correspondence Address: Cristofanilli, M.; Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 710 N Fairbanks Ct, Ste 8-250A, United States; email: Massimo.cristofanilli@nm.org Chemicals/CAS: fulvestrant, 129453-61-8; palbociclib, 571190-30-2, 827022-33-3 Funding details: Celgene Funding details: Novartis Funding details: Chugai Pharmaceutical Funding details: Bristol-Myers Squibb, BMS Funding details: Canada Millennium Scholarship Foundation, CMSF Funding details: Eli Lilly and Company Funding details: GlaxoSmithKline, GSK Funding details: Roche Funding details: Bayer Funding details: Servier Funding details: AstraZeneca Funding details: Genentech Funding text 1: Massimo Cristofanilli has been a consultant or on the advisory board for Domp{\'e} Farmaceutici, Cynvenio Biosystems, Newomics and Vortex Biosciences and received honoraria from Pfizer, Celgene, Domp{\'e} Farmaceutici and Agendia. Angela DeMichele has received honoraria from Pfizer, and her institution received research funding from Genentech, Pfizer, Incyte, Millennium, Bayer, Veridex, Calithera Biosciences, GlaxoSmithKline and Wyeth. Nicholas Turner has received honoraria from and been a consultant or on the advisory board for Pfizer, and his institution has received research funding from Servier, Pfizer, Eli Lilly, Roche and AstraZeneca. Dennis Slamon has served in a leadership position for BioMarin and has stock or other ownership interests in Pfizer. Seock-Ah Im has been a consultant or on the advisory board for AstraZeneca, Novartis, Roche and Spectrum and has received research funding from AstraZeneca. Norikazu Masuda has received honoraria from Chugai, AstraZeneca and Kyowa-Kirin, and his institution received research funding from Chugai, Pfizer, Novartis, Lilly, AstraZeneca and Kyowa-Kirin. Shailendra Verma has been a consultant or on the advisory board for Pfizer. Sherene Loi's institution has received research funding from Roche/Genentech, Pfizer, Novartis, Merck, Puma Biotechnology and Bristol-Myers Squibb. Marco Colleoni has been a consultant or on the advisory board for Pierre Fabre, Pfizer, OBI Pharma, Puma Biotechnology, Celldex and AstraZeneca and received honoraria from Novartis. Kathy Puyana Theall, Xin Huang, Yuan Liu and Cynthia Huang Bartlett are employees of and own stock in Pfizer. Carla Giorgetti was an employee of Pfizer when the manuscript was initiated. Funding text 2: This study was funded by Pfizer Inc . Funding text 3: This study was sponsored by Pfizer Inc, USA . Editorial support was provided by Johna Van Stelten, PhD, and Anny Wu, PharmD, of Complete Healthcare Communications, LLC (North Wales, PA), a CHC Group Company. Appendix A References: Cardoso, F., Costa, A., Norton, L., ESO-ESMO 2nd international consensus guidelines for Advanced Breast Cancer (ABC2) (2014) Ann Oncol, 25, pp. 1871-1888; National Comprehensive Cancer Network, NCCN clinical practice guidelines in oncology (NCCN Guidelines{\circledR}) (2017) Breast Cancer, , https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf, Version 4. Available at: (Accessed 12 February 2018); Hayes, E.L., Lewis-Wambi, J.S., Mechanisms of endocrine resistance in breast cancer: an overview of the proposed roles of noncoding RNA (2015) Breast Cancer Res, 17, p. 40; Turner, N.C., Neven, P., Loibl, S., Andre, F., Advances in the treatment of advanced oestrogen-receptor-positive breast cancer (2017) Lancet, 389, pp. 2403-2414; Cristofanilli, M., Turner, N.C., Bondarenko, I., Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial (2016) Lancet Oncol, 17, pp. 425-439; Finn, R.S., Crown, J.P., Lang, I., The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study (2015) Lancet Oncol, 16, pp. 25-35; Turner, N.C., Ro, J., Andre, F., Palbociclib in hormone-receptor-positive advanced breast cancer (2015) N Engl J Med, 373, pp. 209-219; Hortobagyi, G.N., Stemmer, S.M., Burris, H.A., Ribociclib as first-line therapy for HR-positive, advanced breast cancer (2016) N Engl J Med, 375, pp. 1738-1748; Sledge, G.W., Jr., Toi, M., Neven, P., MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy (2017) J Clin Oncol, 35, pp. 2875-2884; Full prescribing information (2018), http://labeling.pfizer.com/ShowLabeling.aspx?id=2191, Pfizer New York, NY; Kim, E.S., Scott, L.J., Palbociclib: a review in HR-positive, HER2-negative, advanced or metastatic breast cancer (2017) Target Oncol, 12, pp. 373-383; European Medicines Agency, Ibrance hard capsules: summary of product characteristics (2017), http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003853/WC500217196.pdf; Chirila, C., Mitra, D., Colosia, A., Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis (2017) Curr Med Res Opin, pp. 1-25; Kwapisz, D., Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib (2017) Breast Cancer Res Treat, 166, pp. 41-54; Spring, L., Bardia, A., Modi, S., Targeting the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions (2016) Discov Med, 21, pp. 65-74. , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477652/pdf/nihms865194.pdf; Shah, A.N., Cristofanilli, M., The growing role of CDK4/6 inhibitors in treating hormone receptor-positive advanced breast cancer (2017) Curr Treat Options Oncol, 18, p. 6; Boer, K., Fulvestrant in advanced breast cancer: evidence to date and place in therapy (2017) Therapeut Adv Med Oncol, 9, pp. 465-479; Lefebvre, C., Bachelot, T., Filleron, T., Mutational profile of metastatic breast cancers: a retrospective analysis (2016) PLoS Med, 13; Turner, N.C., Finn, R.S., Martin, M., Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases (2018) Ann Oncol, 29, pp. 669-680; Loibl, S., Turner, N.C., Ro, J., Palbociclib combined with fulvestrant in premenopausal women with advanced breast cancer and prior progression on endocrine therapy: PALOMA-3 results (2017) Oncologist, 22, pp. 1028-1038; Verma, S., Bartlett, C.H., Schnell, P., Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: detailed safety analysis from a multicenter, randomized, placebo-controlled, phase 3 study (PALOMA-3) (2016) Oncologist, 21, pp. 1165-1175; Harbeck, N., Iyer, S., Turner, N., Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial (2016) Ann Oncol, 27, pp. 1047-1054; Baselga, J., Campone, M., Piccart, M., Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer (2012) N Engl J Med, 366, pp. 520-529; Piccart, M., Hortobagyi, G.N., Campone, M., Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2 (2014) Ann Oncol, 25, pp. 2357-2362; Yardley, D.A., Noguchi, S., Pritchard, K.I., Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis (2013) Adv Ther, 30, pp. 870-884; Toy, W., Shen, Y., Won, H., ESR1 ligand-binding domain mutations in hormone-resistant breast cancer (2013) Nat Genet, 45, pp. 1439-1445; Jeselsohn, R., Yelensky, R., Buchwalter, G., Emergence of constitutively active estrogen receptor-alpha mutations in pretreated advanced estrogen receptor-positive breast cancer (2014) Clin Cancer Res, 20, pp. 1757-1767; Gupta, S., Zhang, J., Jerusalem, G., The association of chemotherapy versus hormonal therapy and health outcomes among patients with hormone receptor-positive, HER2-negative metastatic breast cancer: experience from the patient perspective (2014) Expert Rev Pharmacoecon Outcomes Res, 14, pp. 929-940; Mamiya, H., Tahara, R.K., Tolaney, S.M., Choudhry, N.K., Najafzadeh, M., Cost-effectiveness of palbociclib in hormone receptor-positive advanced breast cancer (2017) Ann Oncol, 28, pp. 1825-1831; Budczies, J., Bockmayr, M., Denkert, C., Classical pathology and mutational load of breast cancer - integration of two worlds (2015) J Pathol Clin Res, 1, pp. 225-238",
year = "2018",
doi = "10.1016/j.ejca.2018.08.011",
language = "English",
volume = "104",
pages = "21--31",
journal = "European Journal of Cancer",
issn = "0014-2964",
publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer in PALOMA-3

AU - Cristofanilli, M.

AU - DeMichele, A.

AU - Giorgetti, C.

AU - Turner, N.C.

AU - Slamon, D.J.

AU - Im, S.-A.

AU - Masuda, N.

AU - Verma, S.

AU - Loi, S.

AU - Colleoni, M.

AU - Theall, K.P.

AU - Huang, X.

AU - Liu, Y.

AU - Bartlett, C.H.

N1 - Cited By :1 Export Date: 6 February 2019 CODEN: EJCAE Correspondence Address: Cristofanilli, M.; Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 710 N Fairbanks Ct, Ste 8-250A, United States; email: Massimo.cristofanilli@nm.org Chemicals/CAS: fulvestrant, 129453-61-8; palbociclib, 571190-30-2, 827022-33-3 Funding details: Celgene Funding details: Novartis Funding details: Chugai Pharmaceutical Funding details: Bristol-Myers Squibb, BMS Funding details: Canada Millennium Scholarship Foundation, CMSF Funding details: Eli Lilly and Company Funding details: GlaxoSmithKline, GSK Funding details: Roche Funding details: Bayer Funding details: Servier Funding details: AstraZeneca Funding details: Genentech Funding text 1: Massimo Cristofanilli has been a consultant or on the advisory board for Dompé Farmaceutici, Cynvenio Biosystems, Newomics and Vortex Biosciences and received honoraria from Pfizer, Celgene, Dompé Farmaceutici and Agendia. Angela DeMichele has received honoraria from Pfizer, and her institution received research funding from Genentech, Pfizer, Incyte, Millennium, Bayer, Veridex, Calithera Biosciences, GlaxoSmithKline and Wyeth. Nicholas Turner has received honoraria from and been a consultant or on the advisory board for Pfizer, and his institution has received research funding from Servier, Pfizer, Eli Lilly, Roche and AstraZeneca. Dennis Slamon has served in a leadership position for BioMarin and has stock or other ownership interests in Pfizer. Seock-Ah Im has been a consultant or on the advisory board for AstraZeneca, Novartis, Roche and Spectrum and has received research funding from AstraZeneca. Norikazu Masuda has received honoraria from Chugai, AstraZeneca and Kyowa-Kirin, and his institution received research funding from Chugai, Pfizer, Novartis, Lilly, AstraZeneca and Kyowa-Kirin. Shailendra Verma has been a consultant or on the advisory board for Pfizer. Sherene Loi's institution has received research funding from Roche/Genentech, Pfizer, Novartis, Merck, Puma Biotechnology and Bristol-Myers Squibb. Marco Colleoni has been a consultant or on the advisory board for Pierre Fabre, Pfizer, OBI Pharma, Puma Biotechnology, Celldex and AstraZeneca and received honoraria from Novartis. Kathy Puyana Theall, Xin Huang, Yuan Liu and Cynthia Huang Bartlett are employees of and own stock in Pfizer. Carla Giorgetti was an employee of Pfizer when the manuscript was initiated. Funding text 2: This study was funded by Pfizer Inc . Funding text 3: This study was sponsored by Pfizer Inc, USA . Editorial support was provided by Johna Van Stelten, PhD, and Anny Wu, PharmD, of Complete Healthcare Communications, LLC (North Wales, PA), a CHC Group Company. Appendix A References: Cardoso, F., Costa, A., Norton, L., ESO-ESMO 2nd international consensus guidelines for Advanced Breast Cancer (ABC2) (2014) Ann Oncol, 25, pp. 1871-1888; National Comprehensive Cancer Network, NCCN clinical practice guidelines in oncology (NCCN Guidelines®) (2017) Breast Cancer, , https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf, Version 4. Available at: (Accessed 12 February 2018); Hayes, E.L., Lewis-Wambi, J.S., Mechanisms of endocrine resistance in breast cancer: an overview of the proposed roles of noncoding RNA (2015) Breast Cancer Res, 17, p. 40; Turner, N.C., Neven, P., Loibl, S., Andre, F., Advances in the treatment of advanced oestrogen-receptor-positive breast cancer (2017) Lancet, 389, pp. 2403-2414; Cristofanilli, M., Turner, N.C., Bondarenko, I., Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial (2016) Lancet Oncol, 17, pp. 425-439; Finn, R.S., Crown, J.P., Lang, I., The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study (2015) Lancet Oncol, 16, pp. 25-35; Turner, N.C., Ro, J., Andre, F., Palbociclib in hormone-receptor-positive advanced breast cancer (2015) N Engl J Med, 373, pp. 209-219; Hortobagyi, G.N., Stemmer, S.M., Burris, H.A., Ribociclib as first-line therapy for HR-positive, advanced breast cancer (2016) N Engl J Med, 375, pp. 1738-1748; Sledge, G.W., Jr., Toi, M., Neven, P., MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy (2017) J Clin Oncol, 35, pp. 2875-2884; Full prescribing information (2018), http://labeling.pfizer.com/ShowLabeling.aspx?id=2191, Pfizer New York, NY; Kim, E.S., Scott, L.J., Palbociclib: a review in HR-positive, HER2-negative, advanced or metastatic breast cancer (2017) Target Oncol, 12, pp. 373-383; European Medicines Agency, Ibrance hard capsules: summary of product characteristics (2017), http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003853/WC500217196.pdf; Chirila, C., Mitra, D., Colosia, A., Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis (2017) Curr Med Res Opin, pp. 1-25; Kwapisz, D., Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib (2017) Breast Cancer Res Treat, 166, pp. 41-54; Spring, L., Bardia, A., Modi, S., Targeting the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions (2016) Discov Med, 21, pp. 65-74. , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477652/pdf/nihms865194.pdf; Shah, A.N., Cristofanilli, M., The growing role of CDK4/6 inhibitors in treating hormone receptor-positive advanced breast cancer (2017) Curr Treat Options Oncol, 18, p. 6; Boer, K., Fulvestrant in advanced breast cancer: evidence to date and place in therapy (2017) Therapeut Adv Med Oncol, 9, pp. 465-479; Lefebvre, C., Bachelot, T., Filleron, T., Mutational profile of metastatic breast cancers: a retrospective analysis (2016) PLoS Med, 13; Turner, N.C., Finn, R.S., Martin, M., Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases (2018) Ann Oncol, 29, pp. 669-680; Loibl, S., Turner, N.C., Ro, J., Palbociclib combined with fulvestrant in premenopausal women with advanced breast cancer and prior progression on endocrine therapy: PALOMA-3 results (2017) Oncologist, 22, pp. 1028-1038; Verma, S., Bartlett, C.H., Schnell, P., Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: detailed safety analysis from a multicenter, randomized, placebo-controlled, phase 3 study (PALOMA-3) (2016) Oncologist, 21, pp. 1165-1175; Harbeck, N., Iyer, S., Turner, N., Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial (2016) Ann Oncol, 27, pp. 1047-1054; Baselga, J., Campone, M., Piccart, M., Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer (2012) N Engl J Med, 366, pp. 520-529; Piccart, M., Hortobagyi, G.N., Campone, M., Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2 (2014) Ann Oncol, 25, pp. 2357-2362; Yardley, D.A., Noguchi, S., Pritchard, K.I., Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis (2013) Adv Ther, 30, pp. 870-884; Toy, W., Shen, Y., Won, H., ESR1 ligand-binding domain mutations in hormone-resistant breast cancer (2013) Nat Genet, 45, pp. 1439-1445; Jeselsohn, R., Yelensky, R., Buchwalter, G., Emergence of constitutively active estrogen receptor-alpha mutations in pretreated advanced estrogen receptor-positive breast cancer (2014) Clin Cancer Res, 20, pp. 1757-1767; Gupta, S., Zhang, J., Jerusalem, G., The association of chemotherapy versus hormonal therapy and health outcomes among patients with hormone receptor-positive, HER2-negative metastatic breast cancer: experience from the patient perspective (2014) Expert Rev Pharmacoecon Outcomes Res, 14, pp. 929-940; Mamiya, H., Tahara, R.K., Tolaney, S.M., Choudhry, N.K., Najafzadeh, M., Cost-effectiveness of palbociclib in hormone receptor-positive advanced breast cancer (2017) Ann Oncol, 28, pp. 1825-1831; Budczies, J., Bockmayr, M., Denkert, C., Classical pathology and mutational load of breast cancer - integration of two worlds (2015) J Pathol Clin Res, 1, pp. 225-238

PY - 2018

Y1 - 2018

N2 - Background: The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit. Methods: Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174). Baseline characteristics, mutation status and HR expression levels were compared in patients with and without prolonged benefit (treatment duration ≥18 months). Results: By August 2016, 100 patients (29%) on palbociclib-fulvestrant and 26 (15%) on placebo-fulvestrant demonstrated prolonged benefit, with long-term responders in both arms sharing common clinical characteristics. They usually had less disease burden at baseline versus those treated

AB - Background: The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit. Methods: Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174). Baseline characteristics, mutation status and HR expression levels were compared in patients with and without prolonged benefit (treatment duration ≥18 months). Results: By August 2016, 100 patients (29%) on palbociclib-fulvestrant and 26 (15%) on placebo-fulvestrant demonstrated prolonged benefit, with long-term responders in both arms sharing common clinical characteristics. They usually had less disease burden at baseline versus those treated

KW - Advanced breast cancer

KW - Fulvestrant

KW - HR+/HER2–

KW - Long-term response

KW - Palbociclib

KW - estrogen receptor

KW - fulvestrant

KW - palbociclib

KW - placebo

KW - progesterone receptor

KW - adult

KW - aged

KW - Article

KW - cancer hormone therapy

KW - cancer patient

KW - clinical outcome

KW - controlled study

KW - disease burden

KW - esr1 gene

KW - female

KW - gene mutation

KW - human

KW - major clinical study

KW - metastatic breast cancer

KW - multicenter study

KW - mutation rate

KW - pik3ca gene

KW - postmenopause

KW - premenopause

KW - priority journal

KW - randomized controlled trial

KW - treatment response

KW - tumor gene

U2 - 10.1016/j.ejca.2018.08.011

DO - 10.1016/j.ejca.2018.08.011

M3 - Article

VL - 104

SP - 21

EP - 31

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0014-2964

ER -