Abstract
BackgroundClinical trials of human epidermal growth factor receptor 2 (HER2)-targeted agents added to standard treatment have been efficacious for HER2-positive (HER2+) advanced breast cancer. To our knowledge, no meta-analysis has evaluated HER2-targeted therapy including trastuzumab emtansine (T-DM1) and pertuzumab for HER2-positive breast caner and ranked the targeted treatments. We performed a network meta-analysis of both direct and indirect comparisons to evaluate the effect of adding HER2-targeted agents to standard treatment and examined side effects.MethodsWe performed a Bayesian-framework network meta-analysis of randomized controlled trials to compare 6 HER2-targeted treatment regimens and 1 naïve standard treatment (NST, without any-targeted drugs) in targeted treatment of HER2+ breast cancer in adults. These treatment regimens were T-DM1, LC (lapatinib), HC (trastuzumab), PEC (pertuzumab), LHC (lapatinib and trastuzumab), and PEHC (pertuzumab and trastuzumab). The main outcomes were overall survival and response rates. We also examined side effects of rash, LVEF (left ventricular ejection fraction), fatigue, and gastrointestinal disorders, and performed subgroup analysis for the different treatment regimens in metastatic or advanced breast cancer.ResultsWe identified 25 articles of 21 trials, with data for 11,276 participants. T-DM1 and PEHC were more efficient drug regimens with regard to overall survival as compared with LHC, LC, HC and PEC. The incidence of treatment-related rash occurs more frequently in the patients who received LC treatment regimen than PEHC and T-DM1 and HC. In subgroup analysis, T-DM1 was associated with increased overall survival as compared with LC and HC. PEHC was associated with increased overall response as compared with LC, HC, and NST.ConclusionsOverall, the regimen of T-DM1 as well as pertuzumab in combination with trastuzumab and docetaxel is efficacious with fewer side effects as compared with other regimens, especially for advanced HER2+ breast cancer.ImpactThis study suggests that both T-DM1 and PEHC therapy are potentially and equally useful treatments for HER2+ breast cancer.
Highlights
Breast cancer, with more than 1 million new cases confirmed per year in the world[1], is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide
The regimen of T-DM1 as well as pertuzumab in combination with trastuzumab and docetaxel is efficacious with fewer side effects as compared with other regimens, especially for advanced human epidermal growth factor receptor 2 (HER2)+ breast cancer
This study suggests that both T-DM1 and PEHC therapy are potentially and useful treatments for HER2+ breast cancer
Summary
With more than 1 million new cases confirmed per year in the world[1], is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. In addition to the CLEOPATRA study, by far there have been only two randomized clinical trials of combination treatments including more than one of the above HER2-targeted drugs to treat HER2-positive breast cancer patients[22, 23]. No randomized clinical trial has compared a lapatinib-containing regimen directly with pertuzumab-containing or T-DM1-containing regimen, so there is a need for indirect meta-analysis to evaluate these different HER2-targeted therapies. Clinical trials of human epidermal growth factor receptor 2 (HER2)-targeted agents added to standard treatment have been efficacious for HER2-positive (HER2+) advanced breast cancer. No meta-analysis has evaluated HER2-targeted therapy including trastuzumab emtansine (T-DM1) and pertuzumab for HER2-positive breast caner and ranked the targeted treatments. We performed a network meta-analysis of both direct and indirect comparisons to evaluate the effect of adding HER2-targeted agents to standard treatment and examined side effects
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