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Review
. 2013:8:69-78.
doi: 10.2147/CE.S50474. Epub 2013 Sep 30.

Lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in the treatment of HER-2-overexpressing locally advanced or metastatic breast cancer: systematic review and meta-analysis

Tobias Engel Ayer Botrel  1 , Luciano Paladini, Otávio Augusto C Clark
Affiliations
Review

Lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in the treatment of HER-2-overexpressing locally advanced or metastatic breast cancer: systematic review and meta-analysis

Tobias Engel Ayer Botrel et al. Core Evid. 2013.

Abstract

Background: This paper reports a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in human epidermal growth factor receptor 2-overexpressing (HER-2+) locally advanced or metastatic breast cancer.

Methods: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were progression-free survival and overall survival. The side effects of each treatment were analyzed. The data extracted from the studies were combined by using the hazard ratio or risk ratio with their corresponding 95% confidence interval (CI).

Results: A total of 113 references were identified and screened. The final analysis included four trials comprising 1,073 patients with HER-2+. The overall response rate was higher in patients who received the combination of CET plus lapatinib (risk ratio 0.78; 95% CI 0.71-0.85; P < 0.00001) but with significant heterogeneity (χ(2) = 15.61, df = 3; P = 0.001; I(2) = 81%). This result remained favorable to the use of lapatinib when a random-effects model analysis was performed (risk ratio 0.76; 95% CI 0.62-0.94; P = 0.01). Progression-free survival was also higher in patients who received CET plus lapatinib (hazard ratio 0.57; 95% CI 0.49-0.66; P < 0.00001) with no heterogeneity detected on this analysis (χ(2) = 3.05; df = 3; P = 0.38; I(2) = 1%). Overall survival was significantly longer in patients who received CET plus lapatinib (hazard ratio 0.80; 95% CI 0.69-0.92; P = 0.002) without heterogeneity on this analysis (χ(2) = 1.26; df = 3; P = 0.74; I(2) = 0%). Regarding adverse events and severe toxicities (grade ≥3), the group receiving CET plus lapatinib had higher rates of neutropenia (risk ratio 2.08; 95% CI 1.64-2.62; P < 0.00001), diarrhea (risk ratio 4.82; 95% CI 3.14-7.41; P < 0.00001), and rash (risk ratio 8.03; 95% CI 2.46-26.23; P = 0.0006).

Conclusion: The combination of CET plus lapatinib increased the overall response rate, progression-free survival, and overall survival in patients with HER-2+ locally advanced or metastatic breast cancer.

Keywords: breast cancer; chemotherapy; lapatinib; meta-analysis.

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Figures

Figure 1
Figure 1
Trial selection flow. Abbreviation: HER-2, human epidermal growth factor-2.
Figure 2
Figure 2
Comparison of objective response rates on CET with lapatinib versus CET alone. Abbreviations: CET, chemotherapy or endocrine therapy; CI, confidence interval; M–H, Mantel–Haenszel.
Figure 3
Figure 3
Comparison of objective response rates on CET with lapatinib versus CET alone (random-effects model analysis). Abbreviations: CET, chemotherapy or endocrine therapy; CI, confidence interval; M–H, Mantel–Haenszel.
Figure 4
Figure 4
Comparison of progression-free survival on CET with lapatinib versus CET alone. Abbreviations: CET, chemotherapy or endocrine therapy; CI, confidence interval; SE, standard error; IV, inverse variance.
Figure 5
Figure 5
Comparison of overall survival on CET with lapatinib versus CET alone. Abbreviations: CET, chemotherapy or endocrine therapy; CI, confidence interval; SE, standard error; IV, inverse variance.
Figure 6
Figure 6
Comparison of hematologic toxicity (any grade) on CET with lapatinib versus CET alone. Abbreviations: CET, chemotherapy or endocrine therapy; CI, confidence interval; M–H, Mantel–Haenszel.
Figure 7
Figure 7
Comparative effect non-hematologic toxicities (any grade) of chemo- or endocrine therapy (CET) with Lapatinib versus CET alone. Abbreviations: CET, chemotherapy or endocrine therapy; CI, confidence interval; M–H, Mantel–Haenszel.
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