Erika Hamilton1, Javier Cortes2, Ozgur Ozyilkan3, Shin-Cheh Chen4, Katarina Petrakova5, Aleksey Manikhas6, Guy Jerusalem7, Roberto Hegg8, Jens Huober9, Sonya C Chapman10, Yi Lu10, Molly C Hardebeck10, Melissa M Bear10, Erica L Johnston10, Miguel Martin11. 1. Breast and Gynecologic Research Program, Sarah Cannon Research Institute, Tennessee Oncology PLLC, Nashville, TN. Electronic address: ehamilton@tnonc.com. 2. Ramón y Cajal University Hospital, Madrid, Spain; Breast Cancer and Melanoma Group, Oncology Department, Vall d'Hebron Institute of Oncology, Barcelona, Spain. 3. Department of Medical Oncology, Baskent University, Adana, Turkey. 4. Chang Gung Memorial Hospital, Chang Gung University, Linkou, Taoyuan City, Taiwan. 5. Department of Comprehensive Cancer Care, Masarykuv Onkologický Ustav, Brno, Czech Republic. 6. Breast Cancer Department, City Clinical Oncology Center, St. Petersburg, Russia. 7. Department of Medical Oncology, Centre Hospitalier Universitaire, Liège, and Liège University, Liège, Belgium. 8. Hospital Pérola Byington/FMUSP, Centro de Referência da Saúde da Mulher, São Paulo, Brazil. 9. Breast Center, Department of Obstetrics & Gynecology, University of Ulm, Ulm, Germany. 10. Eli Lilly and Company, Indianapolis, IN. 11. Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, CIBERONC, GEICAM, Madrid, Spain.
Abstract
BACKGROUND: Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy. PATIENTS AND METHODS: nextMONARCH is an open-label, controlled, randomized, phase II study of women with endocrine-refractory HR+, HER2- MBC previously treated with chemotherapy. Patients received abemaciclib 150 mg plus tamoxifen 20 mg (A+T), abemaciclib 150 mg every 12 hours (A-150), or abemaciclib 200 mg plus prophylactic loperamide (A-200). The primary objective was progression-free survival (PFS). PFS analyses tested superiority of A+T to A-200 and informal noninferiority of A-150 to A-200. The secondary objectives included the objective response rate (ORR), safety, and pharmacokinetics. RESULTS: The median PFS was 9.1 months for A+T versus 7.4 months for A-200 (hazard ratio, 0.815; 95% confidence interval, 0.556-1.193; P = .293). The A-200 PFS was comparable to that with A-150 at 6.5 months (hazard ratio, 1.045; 95% confidence interval, 0.711-1.535; P = .811). The ORR was 34.6%, 24.1%, and 32.5% for A+T, A-150, and A-200, respectively. No new safety signals were identified. The incidence and severity of diarrhea (62.3%; grade 3, 7.8%) with A-200 was similar to that with A-150 (67.1%; grade 3, 3.8%). The pharmacokinetics were comparable to previous observations. CONCLUSIONS: The addition of tamoxifen to abemaciclib did not significantly improve PFS or ORR compared with abemaciclib monotherapy but confirmed the single-agent activity of abemaciclib in heavily pretreated HR+, HER2- MBC. Dose reductions and antidiarrheal medication generally managed diarrhea while maintaining efficacy.
BACKGROUND: Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy. PATIENTS AND METHODS: nextMONARCH is an open-label, controlled, randomized, phase II study of women with endocrine-refractory HR+, HER2- MBC previously treated with chemotherapy. Patients received abemaciclib 150 mg plus tamoxifen 20 mg (A+T), abemaciclib 150 mg every 12 hours (A-150), or abemaciclib 200 mg plus prophylactic loperamide (A-200). The primary objective was progression-free survival (PFS). PFS analyses tested superiority of A+T to A-200 and informal noninferiority of A-150 to A-200. The secondary objectives included the objective response rate (ORR), safety, and pharmacokinetics. RESULTS: The median PFS was 9.1 months for A+T versus 7.4 months for A-200 (hazard ratio, 0.815; 95% confidence interval, 0.556-1.193; P = .293). The A-200 PFS was comparable to that with A-150 at 6.5 months (hazard ratio, 1.045; 95% confidence interval, 0.711-1.535; P = .811). The ORR was 34.6%, 24.1%, and 32.5% for A+T, A-150, and A-200, respectively. No new safety signals were identified. The incidence and severity of diarrhea (62.3%; grade 3, 7.8%) with A-200 was similar to that with A-150 (67.1%; grade 3, 3.8%). The pharmacokinetics were comparable to previous observations. CONCLUSIONS: The addition of tamoxifen to abemaciclib did not significantly improve PFS or ORR compared with abemaciclib monotherapy but confirmed the single-agent activity of abemaciclib in heavily pretreated HR+, HER2- MBC. Dose reductions and antidiarrheal medication generally managed diarrhea while maintaining efficacy.
Authors: Malinda T West; Thomas Kartika; Ashley R Paquin; Erik Liederbauer; Tony J Zheng; Lucy Lane; Kyaw Thein; Joseph J Shatzel Journal: Curr Probl Cancer Date: 2022-01-10 Impact factor: 3.187
Authors: Sara M Tolaney; Muralidhar Beeram; J Thaddeus Beck; Alison Conlin; E Claire Dees; Shannon L Puhalla; Brent N Rexer; Howard A Burris; Komal Jhaveri; Teresa Helsten; Carlos Becerra; Kevin Kalinsky; Kathleen N Moore; Allison M Manuel; Andrew Lithio; Gregory L Price; Sonya C Chapman; Lacey M Litchfield; Matthew P Goetz Journal: Front Oncol Date: 2022-02-10 Impact factor: 6.244
Authors: Erika Hamilton; Javier Cortes; Ozgur Ozyilkan; Shin-Cheh Chen; Katarina Petrakova; Aleksey Manikhas; Guy Jerusalem; Roberto Hegg; Jens Huober; Wei Zhang; Yanyun Chen; Miguel Martin Journal: Breast Cancer Res Treat Date: 2022-07-12 Impact factor: 4.624