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

2003 ◽  
Vol 21 (11) ◽  
pp. 2101-2109 ◽  
Author(s):  
Henning Mouridsen ◽  
Mikhail Gershanovich ◽  
Yan Sun ◽  
Ramón Pérez-Carrión ◽  
Corrado Boni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Advanced Breast ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Purpose: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer. Patients and Methods: This multicenter phase III trial randomly assigned 916 patients with hormone receptor–positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician’s discretion. This report updates efficacy at a median follow-up of 32 months. Results: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P < .0001), time to treatment failure (median, 9 v 5.7 months, respectively; P < .0001), overall objective response rate (32% v 21%, respectively; P = .0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy (“time to chemotherapy”) was significantly longer (P = .005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P = .001). Conclusion: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.

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

2001 ◽  
Vol 19 (10) ◽  
pp. 2596-2606 ◽  
Author(s):  
Henning Mouridsen ◽  
Mikhail Gershanovich ◽  
Yan Sun ◽  
Ramón Pérez-Carrión ◽  
Corrado Boni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Clinical Benefit ◽  
Advanced Breast ◽  
First Line ◽  
Once Daily ◽  
First Line Therapy ◽  
Line Therapy ◽  
Antiestrogen Therapy

PURPOSE: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal 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 included 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.

BOLERO-2: Efficacy and safety of first-line everolimus plus exemestane in advanced breast cancer.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 152-152 ◽  
Author(s):  
Hope S. Rugo ◽  
Mario Campone ◽  
Michael Gnant ◽  
Patrick Neven ◽  
Barbara Pistilli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Disease Recurrence ◽  
Hazard Ratio ◽  
Advanced Breast ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

152 Background: In the BOLERO-2 study, progression-free survival (PFS) was significantly longer with the combination of everolimus and exemestane (EVE + EXE) compared with placebo and exemestane (PBO + EXE; hazard ratio = 0.45; p < .0001). Consistent efficacy results were observed in all subgroup analyses, such as in patients with visceral metastases and patients with disease recurrence during/after adjuvant therapy. This analysis of BOLERO-2 examines the efficacy of EVE + EXE in the subgroup of patients who received treatment immediately after recurrence during adjuvant therapy (i.e., as first-line therapy in the advanced setting). Methods: BOLERO-2 enrolled patients with hormone receptor–positive (HR+) advanced breast cancer with disease recurrence or progression after prior nonsteroidal aromatase inhibitors and compared EVE (10 mg/d) + EXE (25 mg/d) vs PBO + EXE. The primary end point was PFS by local investigator review. Results: A total of 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37) in the advanced setting. Of these patients, 74% of the EVE + EXE arm and 76% of the PBO + EXE arm had recurred after adjuvant endocrine therapy plus chemotherapy; 26% and 24%, respectively, had recurred after adjuvant endocrine therapy alone. Also, approximately 20% of patients entered the trial after recurring during or within 12 months of adjuvant therapy (21% EVE + EXE vs 16% PBO + EXE). The EVE + EXE group had significantly longer PFS compared with the PBO + EXE group (11.50 vs 4.07 months, respectively; hazard ratio = 0.39; 95% confidence interval, 0.25-0.62). Median PFS remained longer with EVE + EXE versus PBO + EXE, regardless of whether chemotherapy was included with the prior adjuvant hormonal therapy. Similar results were obtained from the analyses based on central review. The safety profile was consistent with the known profiles of each agent. Conclusions: EVE + EXE prolonged PFS in patients with HR+ advanced breast cancer who received treatment as first-line therapy. These results support the combination of EVE + EXE in patients with recurrence after adjuvant therapy. The recently initiated BOLERO-4 study is also evaluating the efficacy of EVE as a first-line therapy in patients with HR+ advanced breast cancer. Clinical trial information: NCT00863655.

Anastrozole Is Superior to Tamoxifen as First-Line Therapy for Advanced Breast Cancer in Postmenopausal Women: Results of a North American Multicenter Randomized Trial

2000 ◽  
Vol 18 (22) ◽  
pp. 3758-3767 ◽  
Author(s):  
J.M. Nabholtz ◽  
A. Buzdar ◽  
M. Pollak ◽  
W. Harwin ◽  
G. Burton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Vaginal Bleeding ◽  
Advanced Breast ◽  
Thromboembolic Events ◽  
First Line ◽  
Once Daily ◽  
First Line Therapy ◽  
Line Therapy

PURPOSE: The efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) and tamoxifen were compared as first-line therapy for advanced breast cancer in 353 postmenopausal women. PATIENTS AND METHODS: The randomized, double-blind, multicenter study was designed to evaluate anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with hormone receptor–positive tumors or tumors of unknown receptor status who were eligible for endocrine therapy. Primary end points were objective response (OR), defined as complete (CR) or partial (PR) response, time to progression (TTP), and tolerability. RESULTS: Anastrozole was as effective as tamoxifen in terms of OR (21% v 17% of patients, respectively), with clinical benefit (CR + PR + stabilization ≥ 24 weeks) observed in 59% of patients on anastrozole and 46% on tamoxifen (two-sided P = .0098, retrospective analysis). Anastrozole had a significant advantage over tamoxifen in terms of TTP (median TTP of 11.1 and 5.6 months for anastrozole and tamoxifen, respectively; two-sided P = .005). The tamoxifen:anastrozole hazards ratio was 1.44 (lower one-sided 95% confidence limit, 1.16). Both treatments were well tolerated. However, thromboembolic events and vaginal bleeding were reported in fewer patients who received anastrozole compared with those who received tamoxifen (4.1% v 8.2% [thromboembolic events] and 1.2% v 3.8% [vaginal bleeding], respectively). CONCLUSION: Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Furthermore, we observed both a significant increase in TTP and a lower incidence of thromboembolic events and vaginal bleeding with anastrozole. These findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with advanced breast cancer.

Anastrozole Versus Tamoxifen as First-Line Therapy for Advanced Breast Cancer in 668 Postmenopausal Women: Results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability Study

2000 ◽  
Vol 18 (22) ◽  
pp. 3748-3757 ◽  
Author(s):  
J. Bonneterre ◽  
B. Thürlimann ◽  
J.F. R. Robertson ◽  
M. Krzakowski ◽  
L. Mauriac ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Vaginal Bleeding ◽  
Advanced Breast ◽  
Thromboembolic Events ◽  
First Line ◽  
Once Daily ◽  
First Line Therapy ◽  
Line Therapy

PURPOSE: To compare the efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) with that of tamoxifen as first-line therapy for advanced breast cancer (ABC) in postmenopausal women. PATIENTS AND METHODS: This randomized, double-blind, multicenter study evaluated the efficacy of anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with tumors that were hormone receptor–positive or of unknown receptor status who were eligible for endocrine therapy. The primary end points were time to progression (TTP), objective response (OR), and tolerability. RESULTS: A total of 668 patients (340 in the anastrozole arm and 328 in the tamoxifen arm) were randomized to treatment and followed-up for a median of 19 months. Median TTP was similar for both treatments (8.2 months in patients who received anastrozole and 8.3 months in patients who received tamoxifen). The tamoxifen:anastrozole hazards ratio was 0.99 (lower one-sided 95% confidence limit, 0.86), demonstrating that anastrozole was at least equivalent to tamoxifen. Anastrozole was also as effective as tamoxifen in terms of OR (32.9% of anastrozole and 32.6% of tamoxifen patients achieved a complete response [CR] or partial response [PR]). Clinical benefit (CR + PR + stabilization of ≥ 24 weeks) rates were 56.2% and 55.5% for patients receiving anastrozole and tamoxifen, respectively. Both treatments were well tolerated. However, incidences of thromboembolic events and vaginal bleeding were reported in fewer patients treated with anastrozole than with tamoxifen (4.8% v 7.3% [thromboembolic events] and 1.2% v 2.4% [vaginal bleeding], respectively). CONCLUSION: Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Together with the lower observed incidence of thromboembolic events and vaginal bleeding, these findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with ABC.

Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer. A phase III study

2000 ◽  
Vol 46 (6) ◽  
pp. 459-466 ◽  
Author(s):  
Dorte Nielsen ◽  
Per Dombernowsky ◽  
Susanne Kornum Larsen ◽  
Ole Paaske Hansen ◽  
Torben Skovsgaard
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Advanced Breast ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Study
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