TY - JOUR
T1 - 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)
AU - Riemsma, Rob
AU - Forbes, Carol A.
AU - Amonkar, Mayur M.
AU - Lykopoulos, Konstantinos
AU - Diaz, Jose R.
AU - Kleijnen, Jos
AU - Rea, Daniel
PY - 2012/8/1
Y1 - 2012/8/1
N2 - 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 lapatinibletrozole, 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)). Lapatinibletrozole 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: Lapatinibletrozole 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 lapatinibletrozole versus other first-line treatments used in this patient population in terms of three main outcomes: 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.
AB - 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 lapatinibletrozole, 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)). Lapatinibletrozole 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: Lapatinibletrozole 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 lapatinibletrozole versus other first-line treatments used in this patient population in terms of three main outcomes: 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.
KW - Advanced or metastatic breast cancer
KW - Aromatase inhibitor
KW - First line treatment
KW - HER2
KW - HR
KW - Lapatinib
UR - http://www.scopus.com/inward/record.url?scp=84864539047&partnerID=8YFLogxK
U2 - 10.1185/03007995.2012.707643
DO - 10.1185/03007995.2012.707643
M3 - Review article
C2 - 22738819
AN - SCOPUS:84864539047
SN - 0300-7995
VL - 28
SP - 1263
EP - 1279
JO - Current Medical Research and Opinion
JF - Current Medical Research and Opinion
IS - 8
ER -