Palbociclib / Letrozole or Fulvestrant in African American Women With HR+ HER2- Breast Cancer

Summary

This study aims to evaluate the hematological safety of palbociclib with letrozole and fulvestrant in African American women with hormone receptor positive HER2 negative advanced breast cancer. Hematological safety is a composite endpoint of episodes of febrile neutropenia and treatment discontinuation due to neutropenia according to current recommendations for management of neutropenia

Timeline

Start

2016-09

Primary completion

2019-12-16

Completion

2021-03-23

Publications

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• Background Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0.
• Background Wood WC, Muss HB, Solin LJ, Olopade OI. Malignant Tumors of the Breast. In: DeVita VT Jr, Hellmann S, Rosenberg SA, editors. Cancer, Principle and Practice of Oncology, 7thEdition, Lippincott Williams and Wilkins; 2005; 1415-1477.
• Background Leung BS, Potter AH. Mode of estrogen action on cell proliferation in CAMA-1 cells: II. Sensitivity of G1 phase population. J Cell Biochem. 1987 Jul;34(3):213-25. doi: 10.1002/jcb.240340307.
• Background Sutherland RL, Hall RE, Taylor IW. Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateau-phase cells. Cancer Res. 1983 Sep;43(9):3998-4006.
• Background Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jaenicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Chaudri-Ross H, Lang R, Wyld P, Bhatnagar A. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 2003 Jun 1;21(11):2101-9. doi: 10.1200/JCO.2003.04.194.
• Background Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, Los G, Slamon DJ. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77. doi: 10.1186/bcr2419.
• Background Schwartz GK, LoRusso PM, Dickson MA, Randolph SS, Shaik MN, Wilner KD, Courtney R, O'Dwyer PJ. Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1). Br J Cancer. 2011 Jun 7;104(12):1862-8. doi: 10.1038/bjc.2011.177. Epub 2011 May 24.
• Background Flaherty KT, Lorusso PM, Demichele A, Abramson VG, Courtney R, Randolph SS, Shaik MN, Wilner KD, O'Dwyer PJ, Schwartz GK. Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer. Clin Cancer Res. 2012 Jan 15;18(2):568-76. doi: 10.1158/1078-0432.CCR-11-0509. Epub 2011 Nov 16.
• Background DeMichele A, Clark AS, Tan KS, Heitjan DF, Gramlich K, Gallagher M, Lal P, Feldman M, Zhang P, Colameco C, Lewis D, Langer M, Goodman N, Domchek S, Gogineni K, Rosen M, Fox K, O'Dwyer P. CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res. 2015 Mar 1;21(5):995-1001. doi: 10.1158/1078-0432.CCR-14-2258. Epub 2014 Dec 11.
• Background Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16.
• Background A study of Palbociclib (PD-0332991) + letrozole vs. letrozole for first line treatment of postmenopausal women with ER/HER2- advanced breast cancer (PALOMA-2). Available at: https://clinicaltrials.gov/ct2/show/NCT01740427. Accessed on August 9, 2015
• Background Turner NC, Huang Bartlett C, Cristofanilli M. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Oct 22;373(17):1672-3. doi: 10.1056/NEJMc1510345. No abstract available.
• Background NIH Policy and Guidelines on The Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001
• Background Chen MS Jr, Lara PN, Dang JH, Paterniti DA, Kelly K. Twenty years post-NIH Revitalization Act: enhancing minority participation in clinical trials (EMPaCT): laying the groundwork for improving minority clinical trial accrual: renewing the case for enhancing minority participation in cancer clinical trials. Cancer. 2014 Apr 1;120 Suppl 7(0 7):1091-6. doi: 10.1002/cncr.28575.
• Background Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007 Apr 3;146(7):486-92. doi: 10.7326/0003-4819-146-7-200704030-00004.
• Background Reich D, Nalls MA, Kao WH, Akylbekova EL, Tandon A, Patterson N, Mullikin J, Hsueh WC, Cheng CY, Coresh J, Boerwinkle E, Li M, Waliszewska A, Neubauer J, Li R, Leak TS, Ekunwe L, Files JC, Hardy CL, Zmuda JM, Taylor HA, Ziv E, Harris TB, Wilson JG. Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet. 2009 Jan;5(1):e1000360. doi: 10.1371/journal.pgen.1000360. Epub 2009 Jan 30.
• Background Hsieh MM, Tisdale JF, Rodgers GP, Young NS, Trimble EL, Little RF. Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy? J Clin Oncol. 2010 Apr 1;28(10):1633-7. doi: 10.1200/JCO.2009.24.3881. Epub 2010 Mar 1. No abstract available.
• Background Hershman D, Weinberg M, Rosner Z, Alexis K, Tiersten A, Grann VR, Troxel A, Neugut AI. Ethnic neutropenia and treatment delay in African American women undergoing chemotherapy for early-stage breast cancer. J Natl Cancer Inst. 2003 Oct 15;95(20):1545-8. doi: 10.1093/jnci/djg073.
• Background Shajahan-Haq AN, Cheema MS, Clarke R. Application of metabolomics in drug resistant breast cancer research. Metabolites. 2015 Feb 16;5(1):100-18. doi: 10.3390/metabo5010100.
• Background Nowicki S, Gottlieb E. Oncometabolites: tailoring our genes. FEBS J. 2015 Aug;282(15):2796-805. doi: 10.1111/febs.13295. Epub 2015 Apr 30.
• Background Gunther UL. Metabolomics Biomarkers for Breast Cancer. Pathobiology. 2015 Sep;82(3-4):153-65. doi: 10.1159/000430844. Epub 2015 Aug 31.
• Background Shajahan-Haq AN, Cook KL, Schwartz-Roberts JL, Eltayeb AE, Demas DM, Warri AM, Facey CO, Hilakivi-Clarke LA, Clarke R. MYC regulates the unfolded protein response and glucose and glutamine uptake in endocrine resistant breast cancer. Mol Cancer. 2014 Oct 23;13:239. doi: 10.1186/1476-4598-13-239.
• Background Asiago VM, Alvarado LZ, Shanaiah N, Gowda GA, Owusu-Sarfo K, Ballas RA, Raftery D. Early detection of recurrent breast cancer using metabolite profiling. Cancer Res. 2010 Nov 1;70(21):8309-18. doi: 10.1158/0008-5472.CAN-10-1319. Epub 2010 Oct 19.
• Background Lowry MC, Gallagher WM, O'Driscoll L. The Role of Exosomes in Breast Cancer. Clin Chem. 2015 Dec;61(12):1457-65. doi: 10.1373/clinchem.2015.240028. Epub 2015 Oct 14.
• Background Yu S, Cao H, Shen B, Feng J. Tumor-derived exosomes in cancer progression and treatment failure. Oncotarget. 2015 Nov 10;6(35):37151-68. doi: 10.18632/oncotarget.6022.
• Background Yu DD, Wu Y, Zhang XH, Lv MM, Chen WX, Chen X, Yang SJ, Shen H, Zhong SL, Tang JH, Zhao JH. Exosomes from adriamycin-resistant breast cancer cells transmit drug resistance partly by delivering miR-222. Tumour Biol. 2016 Mar;37(3):3227-35. doi: 10.1007/s13277-015-4161-0. Epub 2015 Oct 2.
• Background Lv MM, Zhu XY, Chen WX, Zhong SL, Hu Q, Ma TF, Zhang J, Chen L, Tang JH, Zhao JH. Exosomes mediate drug resistance transfer in MCF-7 breast cancer cells and a probable mechanism is delivery of P-glycoprotein. Tumour Biol. 2014 Nov;35(11):10773-9. doi: 10.1007/s13277-014-2377-z. Epub 2014 Jul 31.
• Background Kelly DL, Kreyenbuhl J, Dixon L, Love RC, Medoff D, Conley RR. Clozapine underutilization and discontinuation in African Americans due to leucopenia. Schizophr Bull. 2007 Sep;33(5):1221-4. doi: 10.1093/schbul/sbl068. Epub 2006 Dec 14.
• Background Xiao JF, Varghese RS, Zhou B, Nezami Ranjbar MR, Zhao Y, Tsai TH, Di Poto C, Wang J, Goerlitz D, Luo Y, Cheema AK, Sarhan N, Soliman H, Tadesse MG, Ziada DH, Ressom HW. LC-MS based serum metabolomics for identification of hepatocellular carcinoma biomarkers in Egyptian cohort. J Proteome Res. 2012 Dec 7;11(12):5914-23. doi: 10.1021/pr300673x. Epub 2012 Nov 1.
• Lynce F, Blackburn MJ, Zhuo R, Gallagher C, Hahn OM, Abu-Khalaf M, Mohebtash M, Wu T, Pohlmann PR, Dilawari A, Tiwari SR, Chitalia A, Warren R, Tan M, Shajahan-Haq AN, Isaacs C. Hematologic safety of palbociclib in combination with endocrine therapy in patients with benign ethnic neutropenia and advanced breast cancer. Cancer. 2021 Oct 1;127(19):3622-3630. doi: 10.1002/cncr.33620. Epub 2021 Jun 22.

Drugs

Indications