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Long-term efficacy and safety of letrozole for the adjuvant treatment of early breast cancer in postmenopausal women: a review.

Monnier A - Ther Clin Risk Manag (2009)

Bottom Line: Letrozole also significantly reduces the occurrence of early distant metastases, the most lethal type of recurrence event, which can lead to improved survival.Clinical comparisons of letrozole with both tamoxifen and placebo have also provided important long-term safety data on the use of AIs as adjuvant therapy in PMW with EBC.The weight of clinical evidence indicates that letrozole is a safe and effective option for adjuvant hormonal therapy across all three AI treatment settings.

View Article: PubMed Central - PubMed

Affiliation: Institut Régional Fédératif du Cancer (IFRC), Centre Hospitalier Belfort-Montbéliard, Montbéliard, France.

ABSTRACT
Aromatase inhibitors (AIs) are becoming more widely used than tamoxifen as adjuvant hormonal therapy for postmenopausal women (PMW) with early breast cancer (EBC). It is clear that these drugs offer important efficacy benefits over tamoxifen and differ from tamoxifen in their safety profile. The accepted strategies for adjuvant AI therapy include initial adjuvant treatment following surgery, switching and/or sequencing from prior tamoxifen, and extended adjuvant therapy following the full 5 years of tamoxifen treatment. Among the available AIs, letrozole has been evaluated in large, well-controlled, double-blind clinical trials in the initial adjuvant, extended adjuvant, and more recently, the sequential adjuvant settings. Letrozole is the most potent of the AIs and provides near complete suppression of plasma estrogens in PMW. Letrozole also significantly reduces the occurrence of early distant metastases, the most lethal type of recurrence event, which can lead to improved survival. Clinical comparisons of letrozole with both tamoxifen and placebo have also provided important long-term safety data on the use of AIs as adjuvant therapy in PMW with EBC. The weight of clinical evidence indicates that letrozole is a safe and effective option for adjuvant hormonal therapy across all three AI treatment settings.

No MeSH data available.


Related in: MedlinePlus

Reduction in overall, local, contralateral, and distant metastatic recurrences with letrozole over tamoxifen at early (2 years) follow-up in the Breast International Group 1–98 trial. The corresponding reductions in each type of recurrence are 30.4%, 47.8%, 26.7%, and 30.4%, respectively. Drawn from data of Mauriac et al 2007.19
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f2-tcrm-5-725: Reduction in overall, local, contralateral, and distant metastatic recurrences with letrozole over tamoxifen at early (2 years) follow-up in the Breast International Group 1–98 trial. The corresponding reductions in each type of recurrence are 30.4%, 47.8%, 26.7%, and 30.4%, respectively. Drawn from data of Mauriac et al 2007.19

Mentions: The findings of BIG 1–98 demonstrate the superiority of letrozole over tamoxifen as initial adjuvant therapy in reducing recurrences overall, as well as DM recurrences, and the end point of OS has consistently trended better. Recent evidence indicates that DM are the most common type of early recurrence event (occurring within 2 years of surgery) in patients on tamoxifen,21 and the benefit of letrozole on DM may be especially relevant, as distant recurrences have been associated with reduced OS and death from breast cancer compared with local recurrences.20 A prospectively planned retrospective analysis of BIG 1–98, which focused on early recurrence events (at 2 years), reported DM recurrences to be the predominant recurrence event at this time point, accounting for 74% of all recurrences.19 Letrozole significantly reduced early recurrence risk by 31% over tamoxifen in this analysis (117 events vs 168 events, HR 0.69; P = 0.002), with a 30% absolute reduction in DM events (87 vs 125 events, 2.3% vs 3.3%) (Figure 2).19 Retrospective analysis from the similarly designed ATAC trial showed only a 7% reduction in early (2.5 years) DM events with anastrozole over tamoxifen.22 Notably, a significant effect of anastrozole on DM recurrences among the HR+ patients (N = 5,216) was not observed until after treatment completion, at a median follow-up of 100 months; no improvement in OS has emerged in the ATAC trial, and 5 fewer overall deaths were seen with anastrozole treatment relative to tamoxifen (all cause deaths, 472 vs 477; HR 0.97; P = 0.7).7 In contrast, at 76 months in BIG 1–98 (N = 4,922), there were 40 fewer deaths with letrozole (overall deaths 303 vs 343), and this difference was due to the avoidance of cancer death events, as the number of deaths without a prior cancer event was equal in the two arms (87 and 87 events).5 The findings of BIG 1–98 over time show the importance of reducing early DM events and support the contention that significant reductions in early DM will lead to long-term improvements in OS.23


Long-term efficacy and safety of letrozole for the adjuvant treatment of early breast cancer in postmenopausal women: a review.

Monnier A - Ther Clin Risk Manag (2009)

Reduction in overall, local, contralateral, and distant metastatic recurrences with letrozole over tamoxifen at early (2 years) follow-up in the Breast International Group 1–98 trial. The corresponding reductions in each type of recurrence are 30.4%, 47.8%, 26.7%, and 30.4%, respectively. Drawn from data of Mauriac et al 2007.19
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747391&req=5

f2-tcrm-5-725: Reduction in overall, local, contralateral, and distant metastatic recurrences with letrozole over tamoxifen at early (2 years) follow-up in the Breast International Group 1–98 trial. The corresponding reductions in each type of recurrence are 30.4%, 47.8%, 26.7%, and 30.4%, respectively. Drawn from data of Mauriac et al 2007.19
Mentions: The findings of BIG 1–98 demonstrate the superiority of letrozole over tamoxifen as initial adjuvant therapy in reducing recurrences overall, as well as DM recurrences, and the end point of OS has consistently trended better. Recent evidence indicates that DM are the most common type of early recurrence event (occurring within 2 years of surgery) in patients on tamoxifen,21 and the benefit of letrozole on DM may be especially relevant, as distant recurrences have been associated with reduced OS and death from breast cancer compared with local recurrences.20 A prospectively planned retrospective analysis of BIG 1–98, which focused on early recurrence events (at 2 years), reported DM recurrences to be the predominant recurrence event at this time point, accounting for 74% of all recurrences.19 Letrozole significantly reduced early recurrence risk by 31% over tamoxifen in this analysis (117 events vs 168 events, HR 0.69; P = 0.002), with a 30% absolute reduction in DM events (87 vs 125 events, 2.3% vs 3.3%) (Figure 2).19 Retrospective analysis from the similarly designed ATAC trial showed only a 7% reduction in early (2.5 years) DM events with anastrozole over tamoxifen.22 Notably, a significant effect of anastrozole on DM recurrences among the HR+ patients (N = 5,216) was not observed until after treatment completion, at a median follow-up of 100 months; no improvement in OS has emerged in the ATAC trial, and 5 fewer overall deaths were seen with anastrozole treatment relative to tamoxifen (all cause deaths, 472 vs 477; HR 0.97; P = 0.7).7 In contrast, at 76 months in BIG 1–98 (N = 4,922), there were 40 fewer deaths with letrozole (overall deaths 303 vs 343), and this difference was due to the avoidance of cancer death events, as the number of deaths without a prior cancer event was equal in the two arms (87 and 87 events).5 The findings of BIG 1–98 over time show the importance of reducing early DM events and support the contention that significant reductions in early DM will lead to long-term improvements in OS.23

Bottom Line: Letrozole also significantly reduces the occurrence of early distant metastases, the most lethal type of recurrence event, which can lead to improved survival.Clinical comparisons of letrozole with both tamoxifen and placebo have also provided important long-term safety data on the use of AIs as adjuvant therapy in PMW with EBC.The weight of clinical evidence indicates that letrozole is a safe and effective option for adjuvant hormonal therapy across all three AI treatment settings.

View Article: PubMed Central - PubMed

Affiliation: Institut Régional Fédératif du Cancer (IFRC), Centre Hospitalier Belfort-Montbéliard, Montbéliard, France.

ABSTRACT
Aromatase inhibitors (AIs) are becoming more widely used than tamoxifen as adjuvant hormonal therapy for postmenopausal women (PMW) with early breast cancer (EBC). It is clear that these drugs offer important efficacy benefits over tamoxifen and differ from tamoxifen in their safety profile. The accepted strategies for adjuvant AI therapy include initial adjuvant treatment following surgery, switching and/or sequencing from prior tamoxifen, and extended adjuvant therapy following the full 5 years of tamoxifen treatment. Among the available AIs, letrozole has been evaluated in large, well-controlled, double-blind clinical trials in the initial adjuvant, extended adjuvant, and more recently, the sequential adjuvant settings. Letrozole is the most potent of the AIs and provides near complete suppression of plasma estrogens in PMW. Letrozole also significantly reduces the occurrence of early distant metastases, the most lethal type of recurrence event, which can lead to improved survival. Clinical comparisons of letrozole with both tamoxifen and placebo have also provided important long-term safety data on the use of AIs as adjuvant therapy in PMW with EBC. The weight of clinical evidence indicates that letrozole is a safe and effective option for adjuvant hormonal therapy across all three AI treatment settings.

No MeSH data available.


Related in: MedlinePlus