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

Abstract

To undertake a systematic review of three firstline treatments (letrozole, anastrozole and exemestane) for hormone sensitive advanced or metastatic breast cancer (MBC) in post-menopausal women. We searched six databases from inception up to January 2009 for relevant trials regardless of language or publication status. Randomised controlled clinical trials assessing the safety and efficacy of first-line AIs for post-menopausal women with hormone receptor-positive (HR?, i.e. ER? and/or PgR?) with or without ErbB2 (HER2)-positive MBC, who have not received prior therapy for advanced or metastatic disease were included. Where meta-analysis using direct or indirect comparisons was considered unsuitable for some or all of the data, we employed a narrative synthesis method. Four studies (25 papers) met the inclusion criteria. From the available evidence, it was possible to directly compare the three AIs with tamoxifen. In addition, by using a network meta-analysis it was possible to compare the three AIs with each other. Based on direct evidence, letrozole seemed to be significantly better than tamoxifen in terms of time-toprogression (TTP) (HR = 0.70 (95% CI: 0.60, 0.82)), objective response rate (RR = 0.65 (95% CI: 0.52, 0.82)) and quality-adjusted time without symptoms or toxicity (QTwist difference = 1.5; P \ 0.001). Exemestane seemed significantly superior to tamoxifen in terms of objective response rate (RR = 0.68 (95% CI: 0.53, 0.89)). Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR = 1.42 (95% CI: 1.15, NR)), but not in the other (HR = 1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen. Tamoxifen was associated with significantly more serious adverse events in comparison with exemestane (OR = 0.61 (95% CI: 0.38, 0.97)); while exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR = 2.33 (95% CI: 1.07, 5.11)). Anastrozole was associated with significantly more total adverse events (OR = 1.04 (95% CI: 1.00, 1.09)) and hot flushes (OR = 1.39 (95% CI: 1.03, 1.89)) in comparison with tamoxifen in one trial; however, the other trial showed no significant differences in adverse events between anastrozole and tamoxifen. The indirect comparison of AIs with each other in women with postmenopausal, hormone sensitive advanced or MBC showed that letrozole and exemestane were better in terms of objective response rate than anastrozole; while the more clinically relevant outcomes overall survival (OS) and progression-free survival (PFS) showed no significant differences between AIs. OS and PFS showed no significant differences between AIs and hence based on these results a class effect for all AIs is possible. However, these results are based on indirect comparisons and a network analysis for which the basic assumptions of homogeneity, similarity and consistency were not fulfilled. Therefore, despite the 123Breast Cancer Res Treat (2010) 123:9-24 DOI 10.1007 fact th...

Current medical treatment of estrogen receptor-positive breast cancer

“…In terms of both PFS and OS, there are also advantages of treating patients with AIs compared to other ET, and letrozole seems to be the drug of choice [65,66] . The adverse effects observed using letrozole or anastrozole are similar than that observed with TAM, and the time-to-progression was better [67] . The combination anastrozole and fulvestrant in metastatic ER+ BC was superior to anastrozole alone [41] .…”

“…Most of the AEs is related to the estrogen deprivation [7] . According to a systematic review, TAM was associated with more serious AEs in comparison with AIs, while exemestane caused more frequently musculoskeletal symptoms and hot flushes, but in some trials no [67] . Another meta-analysis showed that patients treated with AIs had increased risk of gastrointestinal symptoms, such as nausea, vomiting and diarrhea, while the incidence of thromboembolic events and vaginal bleeding were decreased compared to other ETs [66] .…”

Hormone Therapy in Breast Cancer: Where do We Stand?

“…Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR=1.42 (95% CI: 1.15, NR)), but not in the other (HR=1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen [48].…”

The changing face of a rare disease: lymphangioleiomyomatosis

“…A potential new therapeutic approach consists of suppressing oestrogen secretion with aromatase inhibitors, especially in post-menopausal women in whom the adrenal glands are the main source of oestrogens [143]. Letrozole is an aromatase inhibitor currently used to treat oestrogen receptor-positive breast cancer.…”