Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer

Nicholas C Turner, Dennis J Slamon, Jungsil Ro, Igor Bondarenko, Seock-Ah Im, Norikazu Masuda, Marco Colleoni, Angela DeMichele, Sherene Loi, Sunil Verma, Hiroji Iwata, Nadia Harbeck, Sibylle Loibl, Fabrice André, Kathy Puyana Theall, Xin Huang, Carla Giorgetti, Cynthia Huang Bartlett, Massimo Cristofanilli

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We report the results of a prespecified analysis of overall survival.

METHODS: We randomly assigned patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified stratification factors of presence or absence of sensitivity to endocrine therapy, presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety.

RESULTS: Among 521 patients who underwent randomization, the median overall survival was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib-fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo-fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the trial regimen occurred in 16% of the patients in the placebo-fulvestrant group. Among 410 patients with sensitivity to previous endocrine therapy, the median overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib-fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo-fulvestrant group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months). The median duration of subsequent therapy was similar in the two groups, and the median time to the receipt of chemotherapy was 17.6 months in the palbociclib-fulvestrant group, as compared with 8.8 months in the placebo-fulvestrant group (hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were observed with 44.8 months of follow-up.

CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib-fulvestrant resulted in longer overall survival than treatment with placebo-fulvestrant. The differences in overall survival in the entire trial group were not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135 .).

Original languageEnglish
Pages (from-to)1926-1936
Number of pages11
JournalThe New England journal of medicine
Volume379
Issue number20
DOIs
Publication statusPublished - Nov 15 2018

Fingerprint

Breast Neoplasms
Survival
Confidence Intervals
Placebos
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase 4
Therapeutics
Hormones
palbociclib
fulvestrant
Safety
Survival Analysis
Random Allocation
Disease-Free Survival
Disease Progression
Recurrence
Drug Therapy
human ERBB2 protein

Keywords

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects
  • Breast Neoplasms/drug therapy
  • Double-Blind Method
  • ErbB Receptors/analysis
  • Estradiol/administration & dosage
  • Female
  • Fulvestrant
  • Humans
  • Middle Aged
  • Piperazines/administration & dosage
  • Protein Kinase Inhibitors/administration & dosage
  • Pyridines/administration & dosage
  • Receptors, Steroid/analysis
  • Survival Analysis

Cite this

Turner, N. C., Slamon, D. J., Ro, J., Bondarenko, I., Im, S-A., Masuda, N., ... Cristofanilli, M. (2018). Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. The New England journal of medicine, 379(20), 1926-1936. https://doi.org/10.1056/NEJMoa1810527

Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. / Turner, Nicholas C; Slamon, Dennis J; Ro, Jungsil; Bondarenko, Igor; Im, Seock-Ah; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Loibl, Sibylle; André, Fabrice; Puyana Theall, Kathy; Huang, Xin; Giorgetti, Carla; Huang Bartlett, Cynthia; Cristofanilli, Massimo.

In: The New England journal of medicine, Vol. 379, No. 20, 15.11.2018, p. 1926-1936.

Research output: Contribution to journalArticle

Turner, NC, Slamon, DJ, Ro, J, Bondarenko, I, Im, S-A, Masuda, N, Colleoni, M, DeMichele, A, Loi, S, Verma, S, Iwata, H, Harbeck, N, Loibl, S, André, F, Puyana Theall, K, Huang, X, Giorgetti, C, Huang Bartlett, C & Cristofanilli, M 2018, 'Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer', The New England journal of medicine, vol. 379, no. 20, pp. 1926-1936. https://doi.org/10.1056/NEJMoa1810527
Turner NC, Slamon DJ, Ro J, Bondarenko I, Im S-A, Masuda N et al. Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. The New England journal of medicine. 2018 Nov 15;379(20):1926-1936. https://doi.org/10.1056/NEJMoa1810527
Turner, Nicholas C ; Slamon, Dennis J ; Ro, Jungsil ; Bondarenko, Igor ; Im, Seock-Ah ; Masuda, Norikazu ; Colleoni, Marco ; DeMichele, Angela ; Loi, Sherene ; Verma, Sunil ; Iwata, Hiroji ; Harbeck, Nadia ; Loibl, Sibylle ; André, Fabrice ; Puyana Theall, Kathy ; Huang, Xin ; Giorgetti, Carla ; Huang Bartlett, Cynthia ; Cristofanilli, Massimo. / Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. In: The New England journal of medicine. 2018 ; Vol. 379, No. 20. pp. 1926-1936.
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title = "Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer",
abstract = "BACKGROUND: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We report the results of a prespecified analysis of overall survival.METHODS: We randomly assigned patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified stratification factors of presence or absence of sensitivity to endocrine therapy, presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety.RESULTS: Among 521 patients who underwent randomization, the median overall survival was 34.9 months (95{\%} confidence interval [CI], 28.8 to 40.0) in the palbociclib-fulvestrant group and 28.0 months (95{\%} CI, 23.6 to 34.6) in the placebo-fulvestrant group (hazard ratio for death, 0.81; 95{\%} CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the trial regimen occurred in 16{\%} of the patients in the placebo-fulvestrant group. Among 410 patients with sensitivity to previous endocrine therapy, the median overall survival was 39.7 months (95{\%} CI, 34.8 to 45.7) in the palbociclib-fulvestrant group and 29.7 months (95{\%} CI, 23.8 to 37.9) in the placebo-fulvestrant group (hazard ratio, 0.72; 95{\%} CI, 0.55 to 0.94; absolute difference, 10.0 months). The median duration of subsequent therapy was similar in the two groups, and the median time to the receipt of chemotherapy was 17.6 months in the palbociclib-fulvestrant group, as compared with 8.8 months in the placebo-fulvestrant group (hazard ratio, 0.58; 95{\%} CI, 0.47 to 0.73; P<0.001). No new safety signals were observed with 44.8 months of follow-up.CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib-fulvestrant resulted in longer overall survival than treatment with placebo-fulvestrant. The differences in overall survival in the entire trial group were not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135 .).",
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author = "Turner, {Nicholas C} and Slamon, {Dennis J} and Jungsil Ro and Igor Bondarenko and Seock-Ah Im and Norikazu Masuda and Marco Colleoni and Angela DeMichele and Sherene Loi and Sunil Verma and Hiroji Iwata and Nadia Harbeck and Sibylle Loibl and Fabrice Andr{\'e} and {Puyana Theall}, Kathy and Xin Huang and Carla Giorgetti and {Huang Bartlett}, Cynthia and Massimo Cristofanilli",
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TY - JOUR

T1 - Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer

AU - Turner, Nicholas C

AU - Slamon, Dennis J

AU - Ro, Jungsil

AU - Bondarenko, Igor

AU - Im, Seock-Ah

AU - Masuda, Norikazu

AU - Colleoni, Marco

AU - DeMichele, Angela

AU - Loi, Sherene

AU - Verma, Sunil

AU - Iwata, Hiroji

AU - Harbeck, Nadia

AU - Loibl, Sibylle

AU - André, Fabrice

AU - Puyana Theall, Kathy

AU - Huang, Xin

AU - Giorgetti, Carla

AU - Huang Bartlett, Cynthia

AU - Cristofanilli, Massimo

PY - 2018/11/15

Y1 - 2018/11/15

N2 - BACKGROUND: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We report the results of a prespecified analysis of overall survival.METHODS: We randomly assigned patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified stratification factors of presence or absence of sensitivity to endocrine therapy, presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety.RESULTS: Among 521 patients who underwent randomization, the median overall survival was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib-fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo-fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the trial regimen occurred in 16% of the patients in the placebo-fulvestrant group. Among 410 patients with sensitivity to previous endocrine therapy, the median overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib-fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo-fulvestrant group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months). The median duration of subsequent therapy was similar in the two groups, and the median time to the receipt of chemotherapy was 17.6 months in the palbociclib-fulvestrant group, as compared with 8.8 months in the placebo-fulvestrant group (hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were observed with 44.8 months of follow-up.CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib-fulvestrant resulted in longer overall survival than treatment with placebo-fulvestrant. The differences in overall survival in the entire trial group were not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135 .).

AB - BACKGROUND: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We report the results of a prespecified analysis of overall survival.METHODS: We randomly assigned patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified stratification factors of presence or absence of sensitivity to endocrine therapy, presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety.RESULTS: Among 521 patients who underwent randomization, the median overall survival was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib-fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo-fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the trial regimen occurred in 16% of the patients in the placebo-fulvestrant group. Among 410 patients with sensitivity to previous endocrine therapy, the median overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib-fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo-fulvestrant group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months). The median duration of subsequent therapy was similar in the two groups, and the median time to the receipt of chemotherapy was 17.6 months in the palbociclib-fulvestrant group, as compared with 8.8 months in the placebo-fulvestrant group (hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were observed with 44.8 months of follow-up.CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib-fulvestrant resulted in longer overall survival than treatment with placebo-fulvestrant. The differences in overall survival in the entire trial group were not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135 .).

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Breast Neoplasms/drug therapy

KW - Double-Blind Method

KW - ErbB Receptors/analysis

KW - Estradiol/administration & dosage

KW - Female

KW - Fulvestrant

KW - Humans

KW - Middle Aged

KW - Piperazines/administration & dosage

KW - Protein Kinase Inhibitors/administration & dosage

KW - Pyridines/administration & dosage

KW - Receptors, Steroid/analysis

KW - Survival Analysis

U2 - 10.1056/NEJMoa1810527

DO - 10.1056/NEJMoa1810527

M3 - Article

VL - 379

SP - 1926

EP - 1936

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 20

ER -