The SystHERs registry: an observational cohort study of treatment patterns and outcomes in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer

BMC Cancer

Debu Tripathy⁷  Hope S Rugo⁴  Peter A Kaufman⁶  Sandra Swain³  Joyce O’Shaughnessy⁵  Mohammad Jahanzeb²  Ginny Mason⁸  Mary Beattie¹  Bongin Yoo¹  Catherine Lai¹  Anthony Masaquel¹  Sara Hurvitz⁹ 

[1] Genentech, Inc, South San Francisco, CA, USA

[2] University of Miami Sylvester Comprehensive Cancer Center Deerfield Campus, Deerfield Beach, FL, USA

[3] Washington Cancer Institute, Medstar Washington Hospital Center, Washington, DC, USA

[4] University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA

[5] Charles A. Sammons Cancer Center, Texas Oncology, The US Oncology Network, Dallas, TX, USA

[6] Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon NH, USA

[7] Keck School of Medicine, University of Southern California, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA

[8] Inflammatory Breast Cancer Research Foundation, West Lafayette, IN, USA

[9] University of California at Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA

关键词: Trastuzumab emtansine;    Trastuzumab;    SystHERs;    Registry;    Pertuzumab;    Patient-reported outcome;    Observational cohort study;    Metastatic breast cancer;    HER2;    Human epidermal growth factor receptor 2;    Ado-trastuzumab emtansine;   

Others  :  858851
DOI  :  10.1186/1471-2407-14-307

 received in 2013-05-30, accepted in 2014-04-23,  发布年份 2014

【 摘 要 】

Background

Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in approximately 20% of invasive breast cancer cases and is associated with a more aggressive disease course than HER2-negative breast cancer. HER2-targeted therapies have altered the natural history of HER2-positive breast cancer, a trend that will likely further improve with the recent approval of new agents. A prospective, observational cohort study was designed and initiated to provide real-world insights into current treatment patterns, long-term survival, and patients’ experiences with initial and subsequent treatments for HER2-positive metastatic breast cancer (MBC).

Methods/Design

The Systematic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs) is a US-based prospective observational cohort study enrolling patients ≥18 years of age with recently diagnosed HER2-positive MBC not previously treated with systemic therapy in the metastatic setting. The primary objective of the study is to identify treatment patterns and clinical outcomes in recently diagnosed patients in a variety of practice settings. Secondary objectives include comparative efficacy, safety, and patient-reported outcomes (PROs). Healthcare resource utilization is an exploratory end point. Tumor tissue and blood sample collection is optional.

The SystHERs registry will enroll approximately 1000 patients over a 3-year period, after which the study will continue for ≥5 years, allowing for a maximum follow-up of 8 years. The treating physician will determine all care and the frequency of visits. PRO measures will be completed at study enrollment and every 90 days. Clinical data will be abstracted quarterly from patient records. The first patient was enrolled in June 2012, and preliminary descriptive data based on 25% to 30% of the final study population are expected at the end of 2013, and as of April 25, 2014, 386 patients are enrolled.

Discussion

SystHERs is expected to provide in-depth data on demographic, clinicopathological, and treatment patterns and their associations with clinical outcomes, PROs, and healthcare resource utilization. Tumor tissue and DNA repositories will also be established for use in future translational research.

Trial registration number

NCT01615068 (ClinicalTrials.gov identifier).

【 授权许可】

   
2014 Tripathy et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN: The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 2009, 14:320-368.
• [2]Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH: Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 2010, 28:92-98.
• [3]Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235:177-182.
• [4]Esteva FJ, Yu D, Hung M-C, Hortobagyi GN: Molecular predictors of response to trastuzumab and lapatinib in breast cancer. Nat Rev Clin Oncol 2010, 7:98-107.
• [5]Alvarez RH, Valero V, Hortobagyi GN: Emerging targeted therapies for breast cancer. J Clin Oncol 2010, 28:3366-3379.
• [6]Hurvitz SA, Hu Y, O'Brien N, Finn RS: Current approaches and future directions in the treatment of HER2-positive breast cancer. Canc Treat Rev 2013, 39:219-229.
• [7]Tripathy D, Slamon DJ, Cobleigh M, Arnold A, Saleh M, Mortimer JE, Murphy M, Stewart SJ: Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol 2004, 22:1063-1070.
• [8]Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D: Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006, 355:2733-2743.
• [9]von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, Maartense E, Zielinski C, Kaufmann M, Bauer W, Baumann KH, Clemens MR, Duerr R, Uleer C, Andersson M, Stein RC, Nekljudova V, Loibl S: Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German Breast Group 26/Breast International Group 03–05 study. J Clin Oncol 2009, 27:1999-2006.
• [10]Blackwell K, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J: Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 study. J Clin Oncol 2012, 30:2585-2592.
• [11]Petrelli F, Barni S: A pooled analysis of 2618 patients treated with trastuzumab beyond progression for advanced breast cancer. Clin Breast Canc 2013, 13:81-87.
• [12]Fabi A, Metro G, Ferretti G, Giannarelli D, Di Cosimo S, Papaldo P, Mottolese M, Carlini P, Felici A, Russillo M, Cognetti F: Do HER-2 positive metastatic breast cancer patients benefit from the use of trastuzumab beyond disease progression? A mono-institutional experience and systematic review of observational studies. Breast 2008, 17:499-505.
• [13]Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, Bianchi G, Cortes J, McNally VA, Ross GA, Fumoleau P, Gianni L: Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol 2010, 28:1138-1144.
• [14]Baselga J, Cortés J, Kim S-B, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM, CLEOPATRA Study Group: Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012, 366:109-119.
• [15]Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J: Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2013, 14:461-471.
• [16]Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
• [17]Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, Tudor IC, Wang LI, Brammer MG, Shing M, Yood MU, Yardley DA: Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Canc Res 2011, 17:4834-4843.
• [18]Rugo H, Kaufman P, Tan-Chiu E, Ulcickas Yood M, Paik S, Yardley D, Brufsky A, Mayer M, Birkner M, Wang L, Brammer M, Tripathy D: Survival of patients with HER2+ metastatic breast cancer and use of trastuzumab following progression: analysis of RegistHER. In Presented at: 31st Annual San Antonio Breast Cancer Symposium. San Antonio, TX; 2008. Abstract 3142
• [19]Tripathy D, Kaufman PA, Brufsky AM, Mayer M, Yood MU, Yoo B, Qhah C, Yardley D, Rugo HS: First-line treatment patterns and clinical outcomes in patients with HER2-positive and hormone receptor-positive metastatic breast cancer from registHER. Oncologist 2013, 18:501-510.
• [20]Kaufman PA, Brufsky AM, Mayer M, Rugo HS, Tripathy D, Yood MU, Feng S, Wang LI, Quah CS, Yardley DA: Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study. Breast Canc Res Treat 2012, 135:875-883.
• [21]Yardley DA, Kaufman PA, Brufsky A, Ulcickas Yood M, Rugo H, Mayer M, Quah C, Yoo B, Tripathy D: Treatment patterns and clinical outcomes for patients with de novo versus recurrent HER2-positive metastatic breast cancer. Breast Canc Res Treat 2014. [Epub ahead of print]
• [22]Yardley D, Tripathy D, Brufsky AM, Rugo HS, Kaufman PA, Mayer M, Magidson J, Yoo B, Quah C, Ulcickas Yood M: Long-term survivor characteristics in HER2-positive metastatic breast cancer from registHER. Br J Canc 2014. doi:10.1038/bjc.2014.174. [Epub ahead of print]
• [23]Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K, the EMILIA Study Group: Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012, 367:1783-1791.
• [24]Berry DA, Cronin KA, Plevritis SK, Fryback DG, Clarke L, Zelen M, Mandelblatt JS, Yakovlev AY, Habbema JD, Feuer EJ, Cancer Intervention and Surveillance Modeling Network (CISNET) Collaborators: Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 2005, 353:1784-1792.
• [25]Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005, 353:1673-1684.
• [26]Awada A, Bozovic-Spasojevic I, Chow L: New therapies in HER2-positive breast cancer: a major step towards a cure of the disease? Canc Treat Rev 2012, 38:494-504.
• [27]National Cancer Institute Cancer Evaluation Program (CTEP): Common Terminology Criteria for Adverse events (CTCAE) and Common Toxicity Criteria (CTC). http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40 webcite
• [28]Basch E, Abernethy AP, Mullins CD, Reeve BB, Smith ML, Coons SJ, Sloan J, Wenzel K, Chauhan C, Eppard W, Frank ES, Lipscomb J, Raymond SA, Spencer M, Tunis S: Recommendations for incorporating patient-reported outcomes into clinical comparative effectiveness research in adult oncology. J Clin Oncol 2012, 30:4249-4255.
• [29]Brady MJ, Cella DF, Mo F, Bonomi AE, Tulsky DS, Lloyd SR, Deasy S, Cobleigh M, Shiomoto G: Reliability and validity of the functional assessment of cancer therapy-breast quality-of-life instrument. J Clin Oncol 1997, 15:974-986.
• [30]Hausheer FH, Schilsky RL, Bain S, Berghorn EJ, Lieberman F: Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Semin Oncol 2006, 33:15-49.
• [31]Armstrong TS, Cohen M, Eriksen L, Cleeland C: Content validity of self-report measurement instruments: an illustration from the development of the brain tumor module of the M. D. Anderson symptom Inventory. Oncol Nurs Forum 2005, 32:669-676.
• [32]De Haes JCJM, Olschewski M, Fayers P, Visser MRM, Cull A, Hopwood P, Sanderman R: The Rotterdam Symptom Checklist (RSCL): a manual. Groningen, the Netherlands: Northern Centre for Healthcare Research; 1996. http://www.rug.nl/research/share/ webcite
• [33]Reilly Associates Health Outcomes Research: Work Productivity and Activity Impairment Questionnaire (WPAI). http://www.reillyassociates.net/index.html webcite
• [34]Sharp L, Timmons A: The financial impact of a cancer diagnosis. 2010. [National Cancer Registry/Irish Cancer Society 2010]
• [35]Wilcoxon F: Individual comparisons by ranking methods. Biom Bull 1945, 1:80-83.
• [36]Kruskal WH, Wallis WA: Use of ranks in one-criterion variance analysis. J Am Stat Assoc 1952, 47:583-621.
• [37]Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958, 53:457-481.
• [38]Cox DR: Regression models and life-tables. J R Stat Soc Ser B 1972, 34:187-220.
• [39]Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001, 344:783-792.
• [40]Lipscomb J, Reeve BB, Clauser SB, Abrams JS, Bruner DW, Burke LB, Denicoff AM, Ganz PA, Gondek K, Minasian LM, O'Mara AM, Revicki DA, Rock EP, Rowland JH, Sgambati M, Trimble EL: Patient-reported outcomes assessment in cancer trials: taking stock, moving forward. J Clin Oncol 2007, 25:5133-5140.
• [41]Kaufman PA, Mayer M, Dreyer NA: Patient-reported outcomes (PRO) in patients with metastatic breast cancer (MBC) from the VIRGO observational cohort study (OCS) [abstract e11051]. J Clin Oncol 2012., 30(Suppl)
• [42]Basch E, Iasonos A, Barz A, Culkin A, Kris MG, Artz D, Fearn P, Speakman J, Farquhar R, Scher HI, McCabe M, Schrag D: Long-term toxicity monitoring via electronic patient-reported outcomes in patients receiving chemotherapy. J Clin Oncol 2007, 25:5374-5380.
• [43]Eroglu Z, Tagawa T, Somlo G: Human epidermal growth factor receptor family-targeted therapies in the treatment of HER2-overexpressing breast cancer. Oncologist 2014, 19:135-150.