Yeon Hee Park1, Tae-Yong Kim2, Gun Min Kim3, Seok Yun Kang4, In Hae Park5, Jee Hyun Kim6, Kyoung Eun Lee7, Hee Kyung Ahn8, Moon Hee Lee9, Hee-Jun Kim10, Han Jo Kim11, Jong In Lee12, Su-Jin Koh13, Ji-Yeon Kim14, Kyung-Hun Lee2, Joohyuk Sohn3, Sung-Bae Kim15, Jin-Seok Ahn14, Young-Hyuck Im14, Kyung Hae Jung15, Seock-Ah Im2. 1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: yhparkhmo@skku.edu. 2. Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. 3. Division of Medical Oncology and Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. 4. Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea. 5. Center for Breast Cancer, National Cancer Center, Goyang, South Korea. 6. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. 7. Department of Hematology and Oncology, Ewha Womans University Hospital, Seoul, South Korea. 8. Division of Medical Oncology and Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea. 9. Department of Internal Medicine, Inha University School of Medicine, Incheon, South Korea. 10. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea. 11. Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Hospital, Cheonan, South Korea. 12. Division of Hematology-Oncology, Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea. 13. Department of Hematology and Oncology, Ulsan University Hospital, Ulsan University College of Medicine, Ulsan, South Korea. 14. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 15. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
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 thecapecitabine 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 withtamoxifen. FUNDING: Pfizer, Shinpoong, and Daewoong Korea and Takeda.
RCT Entities:
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.
Authors: Francesco Schettini; Fabiola Giudici; Mario Giuliano; Massimo Cristofanilli; Grazia Arpino; Lucia Del Mastro; Fabio Puglisi; Sabino De Placido; Ida Paris; Pietro De Placido; Sergio Venturini; Michelino De Laurentis; PierFranco Conte; Dejan Juric; Antonio Llombart-Cussac; Lajos Pusztai; Aleix Prat; Guy Jerusalem; Angelo Di Leo; Daniele Generali Journal: J Natl Cancer Inst Date: 2020-11-01 Impact factor: 13.506
Authors: Christoph Thomssen; Diana Lüftner; Michael Untch; Renate Haidinger; Rachel Würstlein; Nadia Harbeck; Doris Augustin; Susanne Briest; Johannes Ettl; Peter A Fasching; Frank Förster; Christian M Kurbacher; Hans-Joachim Lück; Norbert Marschner; Lothar Müller; Volkmar Müller; Lidia Perlova-Griff; Isabel Radke; Eugen Ruckhäberle; Iris Scheffen; Eva Schumacher-Wulf; Moritz Schwoerer; Dieter Steinfeld-Birg; Katja Ziegler-Löhr Journal: Breast Care (Basel) Date: 2020-02-10 Impact factor: 2.860