Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results

Author:

Loibl Sibylle12,Turner Nicholas C.3,Ro Jungsil4,Cristofanilli Massimo5,Iwata Hiroji6,Im Seock-Ah7,Masuda Norikazu8,Loi Sherene9,André Fabrice10,Harbeck Nadia11,Verma Sunil12,Folkerd Elizabeth3,Puyana Theall Kathy13,Hoffman Justin14,Zhang Ke14,Bartlett Cynthia Huang15,Dowsett Mitchell3

Affiliation:

1. German Breast Group GBG Forschungs GmbH, Neu-Isenburg, Germany

2. Centre for Haematology and Oncology Bethanien, Frankfurt, Germany

3. Royal Marsden Hospital and Institute of Cancer Research, London, UK

4. National Cancer Center, Goyang-si, South Korea

5. Robert H. Lurie Comprehensive Cancer Center Feinberg School of Medicine, Chicago, Illinois, USA

6. Aichi Cancer Center Hospital, Nagoya, Japan

7. Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

8. Breast Oncology, NHO Osaka National Hospital, Osaka-city, Japan

9. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

10. Institut Gustave Roussy, Villejuif, France

11. Brustzentrum der Universität München (LMU), Munich, Germany

12. University of Calgary, Tom Baker Cancer Centre, Calgary, Alberta, Canada

13. Pfizer Oncology, Cambridge, Massachussets, USA

14. Pfizer Inc., San Diego, California, USA

15. Pfizer Inc., Collegeville, Pennsylvania, USA

Abstract

Abstract Background The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET). Patients and Methods One hundred eight premenopausal endocrine-refractory women ≥18 years with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo. This analysis assessed whether the overall tolerable safety profile and significant progression-free survival (PFS) improvement extended to premenopausal women. Potential drug-drug interactions (DDIs) and ovarian suppression with goserelin were assessed via plasma pharmacokinetics and biochemical analyses, respectively. (ClinicalTrials.gov identifier: NCT01942135) Results Median PFS for premenopausal women in the palbociclib (n = 72) versus placebo arm (n = 36) was 9.5 versus 5.6 months, respectively (hazard ratio, 0.50, 95% confidence interval: 0.29–0.87), and consistent with the significant PFS improvement in the same arms for postmenopausal women. Any-grade and grade ≤3 neutropenia, leukopenia, and infections were among the most frequent adverse events reported in the palbociclib arm with concurrent goserelin administration. Hormone concentrations were similar between treatment arms and confirmed sustained ovarian suppression. Clinically relevant DDIs were not observed. Conclusion Palbociclib combined with fulvestrant and goserelin was an effective and well-tolerated treatment for premenopausal women with prior endocrine-resistant HR+/HER2− ABC. Inclusion of both premenopausal and postmenopausal women in pivotal combination ET trials facilitates access to novel drugs for young women and should be considered as a new standard for clinical trial design.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3