Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: Results of a phase III study of the international letrozole breast cancer group

Henning Mouridsen, Mikhail Gershanovich, Yan Sun, Ramón Pérez-Carrión, Corrado Boni, Alain Monnier, Justus Apffelstaedt, Robert Smith, Harm P. Sleeboom, Fritz Jänicke, Anna Pluzanska, Magdolna Dank, Dominique Becquart, Poonamalle P. Bapsy, Eeva Salminen, Ray Snyder, Mercedes Lassus, J. Arnold Verbeek, Beatrix Staffler, Hilary A. Chaudri-RossMargaret Dugan

Research output: Contribution to journalArticle

Abstract

Purpose: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in post-menopausal women with advanced breast cancer. Patients and Methods: Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor- and/or progesterone receptor-positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points in overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability. Results: TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P = .0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P = .0006), as was the rate of clinical benefit (49% v 38%; P = .001). Survival data are currently immature and not reported here. Both treatments were well tolerated. Conclusion: Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.

Original languageEnglish
Pages (from-to)2596-2606
Number of pages11
JournalJournal of Clinical Oncology
Volume19
Issue number10
Publication statusPublished - May 15 2001

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Mouridsen, H., Gershanovich, M., Sun, Y., Pérez-Carrión, R., Boni, C., Monnier, A., Apffelstaedt, J., Smith, R., Sleeboom, H. P., Jänicke, F., Pluzanska, A., Dank, M., Becquart, D., Bapsy, P. P., Salminen, E., Snyder, R., Lassus, M., Verbeek, J. A., Staffler, B., ... Dugan, M. (2001). Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: Results of a phase III study of the international letrozole breast cancer group. Journal of Clinical Oncology, 19(10), 2596-2606.