Abstract
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/m2 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. Funding: Pfizer, Shinpoong, and Daewoong Korea and Takeda.
Original language | English |
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Pages (from-to) | 1750-1759 |
Number of pages | 10 |
Journal | The Lancet Oncology |
Volume | 20 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2019 |
Bibliographical note
Funding Information:This study was supported by three companies that provided the study drugs: Pfizer (exemestane and palbociclib), Shinpoong (capecitabine), and Daewoong Korea and Takeda (leuprolide). We thank the academic contract research organisation in Samsung Medical Center (SMC), the Statistics and Data Center for data management in SMC, and study coordinators from each institute. We also thank the team members who supported this trial, especially Soohyeon Lee for her great support; Seonwoo Kim and Min-JI Kim who did the statistical analysis in SMC; Korean Cancer Study Group Breast Cancer committee members; and study staff at each site. This work was supported by a grant from the South Korean Ministry of Health and Welfare (HA17C0055) and by the South Korean National R&D Program for Cancer Control, Ministry of Health and Welfare (1720150).
Funding Information:
Because the study is still ongoing and other secondary endpoints will be analysed at the end of the study, data cannot be shared at this time. Acknowledgments This study was supported by three companies that provided the study drugs: Pfizer (exemestane and palbociclib), Shinpoong (capecitabine), and Daewoong Korea and Takeda (leuprolide). We thank the academic contract research organisation in Samsung Medical Center (SMC), the Statistics and Data Center for data management in SMC, and study coordinators from each institute. We also thank the team members who supported this trial, especially Soohyeon Lee for her great support; Seonwoo Kim and Min-JI Kim who did the statistical analysis in SMC; Korean Cancer Study Group Breast Cancer committee members; and study staff at each site. This work was supported by a grant from the South Korean Ministry of Health and Welfare ( HA17C0055 ) and by the South Korean National R&D Program for Cancer Control, Ministry of Health and Welfare ( 1720150 ).
Publisher Copyright:
© 2019 Elsevier Ltd