Efficacy of trastuzumab in routine clinical practice and after progression for metastatic breast cancer patients: the observational Hermine study

Jean-Marc Extra, Eric C Antoine, Anne Vincent-Salomon, Thierry Delozier, Pierre Kerbrat, Anne Bethune-Volters, Jean-Paul Guastalla, Marc Spielmann, Louis Mauriac, Jean-Louis Misset, Daniel Serin, Mario Campone, Christophe Hebert, Céline Remblier, Loïc Bergougnoux, Frank Campana, Moïse Namer, Jean-Marc Extra, Eric C Antoine, Anne Vincent-Salomon, Thierry Delozier, Pierre Kerbrat, Anne Bethune-Volters, Jean-Paul Guastalla, Marc Spielmann, Louis Mauriac, Jean-Louis Misset, Daniel Serin, Mario Campone, Christophe Hebert, Céline Remblier, Loïc Bergougnoux, Frank Campana, Moïse Namer

Abstract

Background: The Hermine study observed the use of trastuzumab for metastatic breast cancer (MBC) in routine practice, including patients who received trastuzumab treatment beyond progression (TBP).

Patients and methods: The study observed 623 patients for > or = 2 years. Treatment was given according to oncologists' normal clinical practices. Endpoints included duration of treatment, efficacy, and cardiac safety. The TBP subanalysis compared overall survival (OS) in 177 patients who received first-line trastuzumab and either continued trastuzumab for > or = 30 days following progression or stopped at or before progression.

Results: The median treatment duration was 13.3 months. In the first-, second-, and third-line or beyond treatment groups, the median time to progression (TTP) were 10.3 months, 9.0 months, and 6.3 months, and the median OS times were 30.3 months, 27.1 months, and 23.2 months, respectively. Heart failure was observed in 2.6% of patients, although no cardiac-associated deaths occurred. In the TBP subanalysis, the median OS duration from treatment initiation and time of disease progression were longer in patients who continued receiving trastuzumab TBP (>27.8 months and 21.3 months, respectively) than in those who stopped (16.8 months and 4.6 months, respectively). However, the groups were not completely comparable, because patients who continued trastuzumab TBP had better prognoses at treatment initiation. The median TTP was longer in patients who continued trastuzumab TBP (10.2 months) than in those who stopped (7.1 months).

Conclusion: The Hermine findings confirm that the pivotal trials of first-line trastuzumab treatment in MBC patients are applicable in clinical practice. The subanalysis suggests that trastuzumab TBP offers a survival benefit to MBC patients treated with first-line trastuzumab.

Conflict of interest statement

Disclosures: Jean-Marc Extra: None; Eric C. Antoine: Consultant/advisory role: Roche SAS; Anne Vincent-Salomon: None; Thierry Delozier: None; Pierre Kerbrat: None; Anne Bethune-Volters: None; Jean-Paul Guastalla: Consultant/advisory role: Roche, GlaxoSmithKline; Marc Spielmann: Consultant/advisory role: Roche, AstraZeneca, Novartis; Louis Mauriac: None; Jean-Louis Misset: None; Daniel Serin: None; Mario Campone: None; Christophe Hebert: None; Céline Remblier: None; Loïc Bergougnoux: None; Frank Campana: None; Moïse Namer: None.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Figures

Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials diagram of patients in the Hermine study.
Figure 2.
Figure 2.
Kaplan–Meier curve of time to progression (A) and overall survival (B) in the overall study population. Date of death was not recorded in five patients.
Figure 3.
Figure 3.
Kaplan–Meier plot comparing OS data from patients who continued trastuzumab beyond progression with that of patients who stopped trastuzumab treatment at or prior to progression from initiation of trastuzumab (A) and date of progression (B). Abbreviations: CI, confidence interval; OS, overall survival.
Figure 4.
Figure 4.
Independent prognostic survival factors for first-line trastuzumab in metastatic breast cancer. Abbreviations: CI, confidence interval; ER, estrogen receptor; PgR, progesterone receptor.

References

    1. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17:2639–2648.
    1. Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: A randomised controlled trial. Lancet. 2007;369:29–36.
    1. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–1684.
    1. Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer administered as first-line treatment: The M77001 study group. J Clin Oncol. 2005;23:4265–4274.
    1. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–792.
    1. Goldhirsch A, Coates AS, Gelber RD, et al. First—select the target: Better choice of adjuvant treatments for breast cancer patients. Ann Oncol. 2006;17:1772–1776.
    1. Cook-Bruns N. Retrospective analysis of the safety of Herceptin® immunotherapy in metastatic breast cancer. Oncology. 2001;61(suppl 2):58–66.
    1. Suter TM, Cook-Bruns N, Barton C. Cardiotoxicity associated with trastuzumab (Herceptin®) therapy in the treatment of metastatic breast cancer. Breast. 2004;13:173–183.
    1. Smith IE. Efficacy and safety of Herceptin® in women with metastatic breast cancer: Results from pivotal clinical studies. Anticancer Drugs. 2001;12(suppl 4):S3–S10.
    1. Antoine EC, Extra JM, Vincent-Salomon A, et al. Multiple lines of trastuzumab provide a survival benefit for women with metastatic breast cancer: Results from the Hermine cohort study [abstract 2099] Eur J Cancer. 2007;43(suppl 5):213.
    1. Pietras RJ, Pegram MD, Finn RS, et al. Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs. Oncogene. 1998;17:2235–2249.
    1. Bartsch R, Wenzel C, Hussian D, et al. Analysis of trastuzumab and chemotherapy in advanced breast cancer after the failure of at least one earlier combination: An observational study. BMC Cancer. 2006;6:63.
    1. Fountzilas G, Razis E, Tsavdaridis D, et al. Continuation of trastuzumab beyond disease progression is feasible and safe in patients with metastatic breast cancer: A retrospective analysis of 80 cases by the Hellenic Cooperative Oncology Group. Clin Breast Cancer. 2003;4:120–125.
    1. Gelmon KA, Mackey J, Verma S, et al. Use of trastuzumab beyond disease progression: Observations from a retrospective review of case histories. Clin Breast Cancer. 2004;5:52–58. discussion 59–62.
    1. Montemurro F, Donadio M, Clavarezza M, et al. Outcome of patients with HER2-positive advanced breast cancer progressing during trastuzumab-based therapy. The Oncologist. 2006;11:318–324.
    1. Morabito A, Longo R, Gattuso D, et al. Trastuzumab in combination with gemcitabine and vinorelbine as second-line therapy for HER-2/neu overexpressing metastatic breast cancer. Oncol Rep. 2006;16:393–398.
    1. Stemmler HJ, Kahlert S, Siekiera W, et al. Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC) Onkologie. 2005;28:582–586.
    1. Tripathy D, Slamon DJ, Cobleigh M, et al. Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol. 2004;22:1063–1070.
    1. Bartsch R, Wenzel C, Altorjai G, et al. Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol. 2007;25:3853–3858.
    1. García-Sáenz JA, Martín M, Puente J, et al. Trastuzumab associated with successive cytotoxic therapies beyond disease progression in metastatic breast cancer. Clin Breast Cancer. 2005;6:325–329.
    1. von Minckwitz G, du Bois A, Schmidt M, et al. 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.
    1. Cameron D, Casey M, Press M, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: Updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112:533–543.
    1. Shirane M, Fujimoto-Ouchi K, Sekiguchi F, et al. Preclinical study of continuous administration of trastuzumab as combination therapy after disease progression with trastuzumab monotherapy [abstract 411] Eur J Cancer. 2005;3(suppl):115.
    1. Scaltriti M, Verma C, Guzman M, et al. Lapatinib induces HER2 stabilization and enhances the antitumour activity of trastuzumab in vivo [abstract 2559]. Presented at the American Association of Cancer Research Annual Meeting; April 12–14; San Diego, California. 2008.
    1. Friess T, Scheuer W, Hasmann M. Combinations of trastuzumab with either pertuzumab or bevacizumab show higher efficacy than lapatinib-based combinations against HER2-positive breast cancer xenografts progressing on trastuzumab monotherapy [poster B102]. Presented at the American Association of Cancer Research–National Cancer Institute–European Organization for Research and Treatment of Cancer International Conference: Molecular Targets and Cancer Therapeutics; October 22–26; San Francisco, California. 2007.
    1. O'Shaughnessy J, Blackwell KL, Burstein H, et al. A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy [abstract 1015] J Clin Oncol. 2008;26(15 suppl):44s.
    1. Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: The M.D. Anderson Cancer Center experience. J Clin Oncol. 2006;24:4107–4115.
    1. Pestalozzi BC, Zahrieh D, Price KN, et al. Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG) Ann Oncol. 2006;17:935–944.
    1. Kirsch DG, Ledezma CJ, Mathews CS, et al. Survival after brain metastases from breast cancer in the trastuzumab era [letter] J Clin Oncol. 2005;23(suppl 1):2114–2116. author reply 2116–2117.
    1. Sawrie SM, Meredith RF, Spencer SA, et al. Her2-neu status as a predictor of survival in patients with brain metastases from primary breast adenocarcinoma. Poster 1016 presented at the 43rd ASCO Annual Meeting; June 1–5; Chicago, Illinois, USA. 2007.
    1. Bartsch R, Rottenfusser A, Wenzel C, et al. Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. J Neurooncol. 2007;85:311–317.

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