Superiority of Letrozole to Tamoxifen in the First-Line Treatment of Advanced Breast Cancer: Evidence from Metastatic Subgroups and a Test of Functional Ability

Abstract

Purpose. The letrozole study 025 is a large (n = 907), international, double-blind, randomized, phase III trial in postmenopausal women with advanced breast cancer. This subanalysis compares the efficacies of letrozole and tamoxifen as first-line therapy in postmenopausual women with advanced breast cancer according to site of metastatic lesions and Karnofsky Performance Status (KPS).Materials and Methods. Nine hundred seven patients with advanced breast cancer were randomly assigned to once-daily oral letrozole (2.5 mg; Femara ® ; Novartis Pharma AG; Basel, Switzerland) or tamoxifen (20 mg; Tamofen ® ; Leiras OY; Turku, Finland). Time to progression (TTP) was estimated using the KaplanMeier product-limit method. Treatments were compared by Cox proportional hazards regression models.Results. Letrozole treatment significantly prolonged TTP in all subsets of patients: those with nonvisceral metastases, those with visceral metastases without liver involvement, and those with liver metastases. The reduction in risk of progression ranged from 25%, for patients with nonvisceral metastases, to 36%, for patients with liver metastases. The distributions of baseline KPS scores for both treatment groupsThe Oncologist 2004;9:489-496 www.TheOncologist.com Correspondence: Hilary A. Chaudri-Ross, M.A., DEP, Novartis Pharma AG, WKL-490.1.04, CH-4057 Basel, Switzerland. Telephone: 41-61-696-1758; Fax: 41-61-696-1820; e-mail: hilary_anne.chaudri@pharma.novartis.com Received November 26, 2002; accepted for publication March 23, 2004. ©AlphaMed Press 1083-7159/2004 The Oncologist ® Breast Cancer LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Identify which advanced breast cancer patients in the three subsets studied (with nonvisceral metastases, with visceral metastases without liver involvement, and with liver metastases) responded most favorably to first-line therapy.2. Describe the limitations of first-line treatment in the three subsets of patients with advanced breast cancer.3. Explain how KPS assessment correlates with overall survival in patients with advanced breast cancer with different sites of metastatic lesions.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME by guest on April 27, 2019http://theoncologist.alphamedpress.org/ Downloaded fromThis material is protected by U.S. Copyright law. Unauthorized reproduction is prohibited. For reprints contact: Reprints@AlphaMedPress.com Mouridsen, Sun, Gershanovich et al. 490 were similar (57% had KPS scores ≥90). Time to worsening of 20 points or more in KPS score was significantly longer with letrozole than with tamoxifen, but modest numbers of patients experienced such deterioration (letrozole, 20%, tamoxifen, 22%, in patients without visceral metastases; 23%-24% in patients with liver metastases; and letrozole, 14%, tamoxifen, 30%, in patients with visceral metastases without liver involvement).Conclusion. These data demonstrate the consistent superiority of letro...

Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer

“…The full network included 4 unique studies comparing tamoxifen (20 mg/day) to letrozole [31][32][33][34][35][36][37][38][39][40], anastrozole (TARGET [30,[41][42][43] and North American [29,44] studies), and exemestane [45][46][47][48][49][50][51][52]. One study comparing anastrozole to tamoxifen (40 mg/day) [53] was excluded because the dosage was incomparable to dosages of tamoxifen used in the other studies.…”

Lapatinib and trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone receptor-positive breast cancer which over-expresses human epidermal growth factor 2 (HER2): a systematic review and economic analysis

“…Roche 20 employed an indirect network meta-analyses based on a Bayesian approach, 74 in which a number of different analyses were performed for OS (base case of 12 trials 49,50,[68][69][70][71][77][78][79][80][81][82] ) and PFS (base case of seven trials 49,50,[68][69][70]78,81 ). A number of assumptions were made and tested by sensitivity analyses.…”

“…A number of assumptions were made and tested by sensitivity analyses. These included an assumption that PFS = TTP (which enabled four additional trials 52,77,79,80 to be considered) and that OS findings for the TAnDEM 50 trial based on the RPSFT adjustment should be used in the base case. In addition, for every outcome, the assumption that AIs hold a 'class effect' (i.e.…”

Primary endocrine therapy in locally advanced breast cancers - Nottingham experience

“…Our results also suggest that those with early progression tend to have lower ER score. The role of endocrine agents in ER+ metastatic disease has been well established [26,27]. Locally advanced breast cancers are likely to have micro metastasis at the time of presentation and a proportion develops frank metastasis during their lifetime.…”