Systematic review of lapatinib in combination with letrozole compared with other first-line treatments for hormone receptor positive(HR+) and HER2+ advanced or metastatic breast cancer(MBC).
Curr Med Res Opin
; 28(8): 1263-79, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-22738819
ABSTRACT
BACKGROUND:
Third-generation aromatase inhibitors (letrozole, anastrozole) have shown superior efficacy in early and advanced breast cancer compared with tamoxifen. For HR+, HER2+ MBC, combination of an AI with an anti-HER2 agent (lapatinib or trastuzumab) has shown clinical benefit.METHODS:
Six databases were searched until January 2009 for randomized controlled clinical trials, assessing the safety and efficacy of first-line treatments for postmenopausal women with HR+ and HER2 (ErbB2) positive MBC, who have not received prior therapy for advanced or metastatic disease. Relevant interventions were lapatinib, aromatase inhibitors, tamoxifen, and trastuzumab. Outcomes included overall survival (OS), progression-free-survival (PFS), time-to-progression (TTP), and objective response rate (ORR).RESULTS:
Eighteen studies (62 papers) were included. Lapatinib + letrozole was significantly superior to letrozole alone based on a direct head-to-head study in terms of PFS/TTP and ORR. Using a network meta-analysis, compared with lapatinib + letrozole, tamoxifen (HR = 0.45 (95% CI 0.32, 0.65) and anastrozole (HR = 0.53 (0.36, 0.80)) scored significantly worse in terms of PFS/TTP and ORR (tamoxifen OR = 0.25 (0.12, 0.53), anastrozole OR = 0.27 (0.12, 0.58). The combination also seemed significantly superior to exemestane in terms of PFS/TTP (HR = 0.52 (0.34, 0.79)). Lapatinib + letrozole also seemed better, although not significantly, in terms of OS versus tamoxifen HR = 0.74 (0.49, 1.12), anastrozole HR = 0.71 (0.45, 1.14) and exemestane HR = 0.65 (0.39, 1.11). When compared with trastuzumab + anastrozole, lapatinib + letrozole seemed to be better in terms of OS (HR = 0.85 (0.47, 1.54)), PFS/TTP (HR = 0.89 (0.54, 1.47)) and ORR (OR = 0.92 (0.24, 3.48)), although, none of these results were significant.DISCUSSION:
Lapatinib + letrozole was significantly superior to letrozole in terms of PFS/TTP and ORR based on a direct head-to-head study. Indirect comparisons appeared to favor lapatinib + letrozole versus other first-line treatments used in this patient population in terms of three mainoutcomes:
OS, PFS/TTP and ORR. Indirect comparison results are based on a network analysis for which the basic assumptions of homogeneity, similarity and consistency were not fulfilled. Therefore, despite the fact that these are the best available data, the results need to be interpreted with caution.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Triazóis
/
Neoplasias da Mama
/
Carcinoma
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Receptores Citoplasmáticos e Nucleares
/
Receptor ErbB-2
/
Nitrilas
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article