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Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial

  • 주제(기타) Oncology
  • 설명문(일반) [Park, Yeon Hee; Kim, Tae-Yong; Ahn, Jin-Seok] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Seoul 06351, South Korea; [Kim, Tae-Yong; Lee, Kyung-Hun; Im, Seock-Ah] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul Natl Univ Hosp,Canc Res Inst, Seoul, South Korea; [Kim, Gun Min; Sohn, Joohyuk] Yonsei Univ, Coll Med, Div Med Oncol, Seoul, South Korea; [Kim, Gun Min; Sohn, Joohyuk] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea; [Kang, Seok Yun] Ajou Univ, Sch Med, Dept Hematol Oncol, Suwon, South Korea; [Park, In Hae] Natl Canc Ctr, Ctr Breast Canc, Goyang, South Korea; [Kim, Jee Hyun] Seoul Natl Univ, Bundang Hosp, Coll Med, Dept Internal Med, Seongnam, South Korea; [Lee, Kyoung Eun] Ewha Womans Univ Hosp, Dept Hematol & Oncol, Seoul, South Korea; [Ahn, Hee Kyung] Gachon Univ, Gil Med Ctr, Div Med Oncol, Incheon, South Korea; [Ahn, Hee Kyung] Gachon Univ, Gil Med Ctr, Dept Internal Med, Incheon, South Korea; [Lee, Moon Hee] Inha Univ, Sch Med, Dept Internal Med, Incheon, South Korea; [Kim, Hee-Jun] Chung Ang Univ, Coll Med, Dept Internal Med, Seoul, South Korea; [Kim, Hee-Jun; Kim, Han Jo] Soonchunhyang Univ Hosp, Div Hematol & Oncol, Dept Internal Med, Cheonan, South Korea; [Lee, Jong In] Yonsei Univ, Wonju Coll Med, Wonju Severance Christian Hosp, Div Hematol Oncol,Dept Internal Med, Wonju, South Korea; [Koh, Su-Jin] Ulsan Univ, Coll Med, Dept Hematol & Oncol, Ulsan Univ Hosp, Ulsan, South Korea; [Kim, Sung-Bae; Jung, Kyung Hae] Univ Ulsan, Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea
  • 등재 SCIE, SCOPUS
  • 발행기관 ELSEVIER SCIENCE INC
  • 발행년도 2019
  • 총서유형 Journal
  • URI http://www.dcollection.net/handler/ewha/000000166029
  • 본문언어 영어
  • Published As http://dx.doi.org/10.1016/S1470-2045(19)30565-0
  • PubMed https://pubmed.ncbi.nlm.nih.gov/31668850

초록/요약

Background Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m(2) twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov, NCT02592746, and is ongoing for follow-up of overall survival. Findings Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9-22), median progression-free survival was 20.1 months (95% CI 14.2-21.8) in the palbociclib plus endocrine therapy group versus 14.4 months (12.1-17.0) in the capecitabine group (hazard ratio 0.659 [95% CI 0.437-0.994], one-sided log-rank p=0.0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 [75%] of 92 vs 14 [16%] of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred. Interpretation Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

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