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

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Anders Wilder Erickson ◽  
Steven Habbous ◽  
Christianne Hoey ◽  
Katarzyna J. Jerzak ◽  
Sunit Das
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Meta Analysis ◽  
Single Agent ◽  
Controlled Trials ◽  
Her2 Positive ◽  
Randomized Controlled ◽  
Dual Versus ◽  
Intracranial Metastatic Disease ◽  
Positive Breast Cancer

AbstractObservational studies have suggested that HER2 inhibition with trastuzumab may be associated with an increased incidence of intracranial metastatic disease (IMD) due to its ability to prolong survival. We hypothesized that prolonged survival associated with dual-agent HER2 inhibition may be associated with an even higher incidence of IMD. This study pooled estimates of IMD incidence and survival among patients with HER2-positive breast cancer receiving dual- versus single-agent HER2 targeted therapy, as well as trastuzumab versus chemotherapy, observation, or another HER2-targeted agent. We searched PubMed, EMBASE, and CENTRAL from inception to 25 March 2020. We included randomized controlled trials that reported IMD incidence for patients with HER2-positive breast cancer receiving trastuzumab as the experimental or control arm irrespective of disease stage. Among 465 records identified, 19 randomized controlled trials (32,572 patients) were included. Meta-analysis of four studies showed that dual HER2-targeted therapy was associated with improved overall survival (HR 0.76; 95% CI, 0.66–0.87) and progression-free survival (HR 0.77; 95% CI, 0.68–0.87) compared to single HER2-targeted therapy, but the risk of IMD was similar (RR 1.03; 95% CI, 0.83–1.27). Our study challenges the hypothesis that prolonged survival afforded by improved extracranial disease control is associated with increased IMD incidence.

scholarly journals HER2-targeted therapy prolongs survival in patients with HER2-positive breast cancer and intracranial metastatic disease: a systematic review and meta-analysis

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Anders W Erickson ◽  
Farinaz Ghodrati ◽  
Steven Habbous ◽  
Katarzyna J Jerzak ◽  
Arjun Sahgal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Metastatic Disease ◽  
Response Rate ◽  
Meta Analysis ◽  
Adverse Event Rate ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Intracranial Metastatic Disease ◽  
Positive Breast Cancer

Abstract Background Intracranial metastatic disease (IMD) is a serious and known complication of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The role of targeted therapy for patients with HER2-positive breast cancer and IMD remains unclear. In this study, we sought to evaluate the effect of HER2-targeted therapy on IMD from HER2-positive breast cancer. Methods We searched MEDLINE, EMBASE, CENTRAL, and gray literature sources for interventional and observational studies reporting survival, response, and safety outcomes for patients with IMD receiving HER2-targeted therapy. We pooled outcomes through meta-analysis and examined confounder effects through forest plot stratification and meta-regression. Evidence quality was evaluated using GRADE (PROSPERO CRD42020161209). Results A total of 97 studies (37 interventional and 60 observational) were included. HER2-targeted therapy was associated with prolonged overall survival (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.39–0.56) without significantly prolonged progression-free survival (HR 0.52; 95% CI, 0.27–1.02) versus non-targeted therapy; the intracranial objective response rate was 19% (95% CI, 12–27%), intracranial disease control rate 62% (95% CI, 55–69%), intracranial complete response rate 0% (95% CI, 0–0.01%), and grade 3+ adverse event rate 26% (95% CI, 11–45%). Risk of bias was high in 40% (39/97) of studies. Conclusion These findings support a potential role for systemic HER2-targeted therapy in the treatment of patients with IMD from HER2-positive metastatic breast cancer.

scholarly journals Dual HER2 Blockade versus a Single Agent in Trastuzumab-Containing Regimens for HER2-Positive Early Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Liuwen Yu ◽  
Fangmeng Fu ◽  
Jing Li ◽  
Meng Huang ◽  
Bangwei Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Controlled Trials ◽  
Hormone Receptor ◽  
Meta Analysis ◽  
Single Agent ◽  
Hormone Receptor Status ◽  
Controlled Trials ◽  
Her2 Positive ◽  
Free Survival ◽  
Randomized Controlled

Purpose. Although trastuzumab is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)- positive early breast cancer (EBC), drug resistance and disease relapse occur. Therefore, we performed a meta-analysis to assess the efficacy and safety of trastuzumab-containing dual anti-HER2 therapy compared to trastuzumab alone. Methods. A systematic search was performed to identify eligible randomized controlled trials (RCTs). Main outcomes including event-free survival/invasive disease-free survival (EFS/iDFS), overall survival (OS), and safety were considered. Results. Ten RCTs were included (15,284 patients). Significant improvements were observed in both EFS/iDFS (HR 0.86, p=0.0003) and OS (HR 0.86, p=0.02) with trastuzumab-based dual anti-HER2 therapy, especially in adjuvant treatment, while in the neoadjuvant setting, dual-targeted therapy also achieved a substantial pathological complete response (pCR) benefit (HR 1.34, p=0.0002). Subgroup analysis revealed that the EFS/iDFS benefit was slightly higher with trastuzumab plus pertuzumab or plus neratinib than trastuzumab plus lapatinib, while OS benefit was significant with trastuzumab plus lapatinib, but there were no subgroup differences (interaction test, p=0.80 and 0.24, resp.). In addition, EFS/iDFS benefit was unrelated to hormone receptor status but pronounced in the lymph node-positive (LN+) subgroup, which should be interpreted cautiously for lacking interaction (p=0.18). Besides, patients receiving dual therapy, especially with the lapatinib-containing regimen, experienced more toxicity, but no increase in cardiotoxicity. Conclusions. Despite being associated with more toxicity, trastuzumab-containing dual anti-HER2 therapy is superior to trastuzumab single agent for HER2-positive EBC independent of hormone receptor status. The correlation between survival and LN status needs further verification. Trastuzumab plus pertuzumab or plus neratinib is the preferred regimen with substantial efficacy and lower toxicity.

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