Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL

被引：98

作者：

Martin, M. ^{[1
,2
,3
]}

Zielinski, C. ^{[4
,5
]}

Ruiz-Borrego, M. ^{[3
,6
]}

Carrasco, E. ^{[3
]}

Turner, N. ^{[7
]}

Ciruelos, E. M. ^{[3
,8
,9
,10
]}

Munoz, M. ^{[3
,11
,12
]}

Bermejo, B. ^{[2
,3
,13
,14
]}

Margeli, M. ^{[3
,15
]}

Anton, A. ^{[2
,3
,16
]}

Kahan, Z. ^{[17
]}

Csoszi, T. ^{[18
]}

Casas, M., I ^{[3
]}

Murillo, L. ^{[3
,19
]}

Morales, S. ^{[3
,20
]}

Alba, E. ^{[2
,3
,21
]}

Gal-Yam, E. ^{[22
]}

Guerrero-Zotano, A. ^{[3
,23
]}

Calvo, L. ^{[3
,24
]}

de la Haba-Rodriguez, J. ^{[2
,3
,25
]}

Ramos, M. ^{[3
,26
]}

Alvarez, I ^{[3
,27
]}

Garcia-Palomo, A. ^{[3
,28
]}

Bartlett, C. Huang ^{[29
]}

Koehler, M. ^{[29
,30
]}

Caballero, R. ^{[3
]}

Corsaro, M. ^{[31
]}

Huang, X. ^{[29
]}

Garcia-Saenz, J. A. ^{[3
,32
]}

Chacon, J., I ^{[3
,33
]}

Swift, C. ^{[34
]}

Thallinger, C. ^{[5
,35
]}

Gil-Gil, M. ^{[3
,36
,37
]}

机构：

[1] Univ Complutense, Inst Invest Sanitaria Gregorio Maranon, Med Dept, Med Oncol, Madrid, Spain

[2] Oncol Biomed Res Natl Network CIBERONC ISCIII, Madrid, Spain

[3] GEICAM Spanish Breast Canc Grp, Madrid, Spain

[4] Wiener Privatklin Hosp, Cent European Canc Ctr, Med Oncol, Vienna, Austria

[5] CECOG Cent European Cooperat Oncol Grp, Vienna, Austria

[6] Hosp Univ Virgen Rocio, Med Oncol, Seville, Spain

[7] Inst Canc Res & Royal Marsden, London, England

[8] Hosp Univ 12 Octubre, Med Oncol, Barcelona, Spain

[9] HM Hosp Madrid, Med Oncol, Madrid, Spain

[10] SOLTI Grp Breast Canc Res, Barcelona, Spain

[11] Hosp Clin Barcelona, Med Oncol, Barcelona, Spain

[12] Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain

[13] Hosp Clin Univ Valencia, Med Oncol, Valencia, Spain

[14] Biomed Res Inst INCLIVA, Valencia, Spain

[15] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, B ARGO Grp, Badalona, Spain

[16] Hosp Univ Miguel Servet, Med Oncol, Zaragoza, Spain

[17] Univ Szeged, Dept Oncotherapy, Szeged, Hungary

[18] Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz R, Dept Oncol, Szolnok, Hungary

[19] Hosp Clin Zaragoza Lozano Blesa, Med Oncol, Zaragoza, Spain

[20] Hosp Arnau Vilanova, Med Oncol, Lleida, Spain

[21] Hosp Reg & Virgen Victoria, IBIMA, UGCI Med Oncol, Malaga, Spain

[22] Sheba Med Ctr, Inst Oncol, Dept Oncol, Tel Hashomer, Israel

[23] Inst Valenciano Oncol, Med Oncol, Valencia, Spain

[24] Complejo Hosp A Coruna, Med Oncol, Coruna, Spain

[25] Hosp Univ Reina Sofia, Med Oncol, Cordoba, Spain

[26] Ctr Oncol Galicia, La Coruna, Coruna, Spain

[27] Hosp Univ Donostia Biodonostia, Med Oncol, San Sebastian, Spain

[28] Hosp Leon, Med Oncol, Leon, Spain

[29] Pfizer, New York, NY USA

[30] Repare Therapeut, Cambridge, MA USA

[31] Pfizer, Milan, Italy

[32] Hosp Clin Univ San Carlos, Med Oncol, Madrid, Spain

[33] Hosp Virgen Salud, Med Oncol, Toledo, Spain

[34] Royal Marsden, Ralph Lauren Ctr Breast Canc Res, London, England

[35] Med Univ Vienna, Dept Oncol, Vienna, Austria

[36] Inst Catala Oncol ICO, Barcelona, Spain

[37] IDIBELL, Barcelona, Spain

来源：

ANNALS OF ONCOLOGY | 2021年 / 32卷 / 04期

关键词：

palbociclib; capecitabine; metastatic breast cancer; hormone receptor-positive; HER2-negative; endocrine therapy; EUROPEAN-ORGANIZATION; FULVESTRANT; MULTICENTER; ABEMACICLIB; PACLITAXEL;

D O I：

10.1016/j.annonc.2020.12.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. Patients and methods: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to Als, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. Results: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). Conclusions: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.

引用

页码：488 / 499

页数：12

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