Risk of severe diarrhea with dual anti-HER2 therapies: a meta-analysis

Although promising progress has been made with dual HER2 blockade in patients with HER2-positive breast cancer, whether the strategy of combined HER2 blockade increases the risk of severe diarrhea remains inclusive. In the present study, we investigated the overall incidence and risk of severe diarrhea when patients were treated with a combination of anti-HER2 therapies compared to anti-HER2 monotherapy. Studies that evaluated the administration of an anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination therapy (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer were identified from the PubMed database (1966-2013), the Cochrane library, abstracts presented at the American Society of Clinical Oncology annual conference (2004-2013), and the Web of Science database (1998-2013). Eligible studies were those in which the only systematic difference between the study arms was the type of anti-HER2 therapy used. Incidence, relative risk (RR), and 95% confidence intervals (CIs) were calculated using random effects or fixed-effects models based on the heterogeneity of the included studies. Seven trials were considered eligible. The overall incidence results for severe diarrhea in the combined anti-HER2 therapy and the anti-HER2 monotherapy were 3.48% (95% CI: 11.60-15.37%) and 8.68% (9 % CI: 7.33-10.03%), respectively. The odds ratio (OR) of severe diarrhea between anti-HER2 combination therapy and monotherapy was 1.67 (95% CI: 1.38 -5.57, p = 0.00001). This meta-analysis provides evidence that the incidence rates of severe diarrhea are comparable between anti-HER2 combination therapy and anti-HER2 monotherapy.