Effects of lapatinib or trastuzumab, alone and in combination, in human epidermal growth factor receptor 2‐positive breast cancer: a meta‐analysis of randomized controlled trials

Abstract

This meta‐analysis compared the efficiency and safety of lapatinib and trastuzumab, alone or in combination, administered with neoadjuvant chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)‐positive breast cancer. For dichotomous variables, the relative risk ratio (RR) and 95% confidence interval (CI) were used to investigate outcome measures: pathological complete response (pCR), neutropenia, diarrhea, dermatologic toxicity, and congestive heart failure (CHF). Eight randomized controlled trials of 2350 participants (837 receiving lapatinib, 913 trastuzumab, and 555 combination therapy) were selected to compare the efficiency and safety of lapatinib to trastuzumab. A significant difference was found between lapatinib and trastuzumab for pCR (RR = 0.82, 95% CI: 0.73–0.93; Z = 3.00; P = 0.003). In six studies, a significant difference was found between trastuzumab and combination therapy for pCR (RR = 1.33, 95% CI: 1.18–1.50; Z = 4.70; P < 0.00001), diarrhea (RR = 14.59, 95% CI: 7.69–27.67; Z = 8.20; P < 0.00001), and dermatologic toxicity (RR = 3.10, 95% CI: 1.61–5.96; Z = 3.39; P = 0.007), but none was found for neutropenia (RR = 1.38, 95% CI: 0.82–2.31; Z = 1.22; P = 0.22) or CHF (RR = 0.14, 95% CI: 0.02–1.17; Z = 1.02; P = 0.07). Combination therapy compared to trastuzumab alone increases the pCR rate of HER2‐positive breast cancer patients with no additional cardiac events. Trastuzumab, which is still the first‐line therapy in breast cancer, increases the pCR rate more than lapatinib.

Comparison of adverse effects of trastuzumab with other drug combinations for the treatment of breast cancer: A review

“…[40] Similar results are also shown by Xin et al and Xu et al that is, the use of lapatinib and trastuzumab in HER2-positive BC cause skin rash, diarrhoea, neutropenia, and hepatic and other AEs. [49,50] Gianni L, Dafni U, et al found that cardiac toxicity was comparable between anti-HER2 combination therapy and anti-HER2 monotherapy. [51] As we have seen that the previous studies only reported about cardiovascular AEs related to trastuzumab but our study concluded all the systemic AEs along with cardiovascular, more often cardiotoxicity when TKi is given combined with chemotherapy, other systemic toxicities also occur.…”

Dual- versus single-agent HER2 inhibition and incidence of intracranial metastatic disease: a systematic review and meta-analysis

“…While other meta-analyses have assessed survival and safety between dual- and single-agent HER2-targeted regimens 77 – 79 , our study compares IMD incidence in these groups and provides the most recent update on the risk of IMD incidence following trastuzumab monotherapy. Our data suggest prolonged survival may not be associated with increased risk of IMD incidence when comparing dual to single HER2-targeted therapy, and when comparing trastuzumab to chemotherapy and observation in early stage disease.…”

A HER2 bispecific antibody can be efficiently expressed in Escherichia�coli with potent cytotoxicity

“…Antibodies or small molecule inhibitors have exhibited clinical efficacy by inhibiting HER2 activity. Besides functioning as an oncogene, HER2 also presents as an excellent tumor antigen, as it is overexpressed in numerous tumors and is rarely expressed in normal tissues (4,8,(43)(44)(45)(46). Vaccines, bispecific antibodies and other approaches have been studied to further improve the clinical outcomes of current HER2 therapeutics.…”

“…Different formats of anti-HER2 bispecific antibodies have been studied previously (15,25,28,45,47,48), including recruitment of T cells in various bispecific antibody formats (17,19,49,50). However, those bispecific antibodies present a number of challenges, including a mixed population during purification, a low yield of production, a tendency to aggregate and a short half-life.…”