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BMC Cancer Oct 2019Although the dual anti-HER2 therapy, namely, pertuzumab plus trastuzumab and docetaxel, has shown promising results in HER2+ breast cancer patients, whether the dose,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although the dual anti-HER2 therapy, namely, pertuzumab plus trastuzumab and docetaxel, has shown promising results in HER2+ breast cancer patients, whether the dose, efficacy and safety of this treatment differs from those of other pertuzumab-based dual anti-HER2 therapies remain controversial. This systematic review evaluates the efficacy and safety of H (trastuzumab or trastuzumab emtansine ± chemotherapy) + P (pertuzumab) compared with those of H in HER2+ breast cancer patients.
METHODS
A comprehensive search was performed to identify eligible studies comparing the efficacy and safety of H + P versus H. The pathologic complete response (pCR), median progression-free survival (PFS) and overall survival (OS) were the primary outcomes, and safety was the secondary outcome. A subgroup analysis of pCR according to hormone receptor (HR) status was performed. All analyses were conducted using STATA 11.0.
RESULTS
Twenty-six studies (9872 patients) were identified. In the neoadjuvant setting, H + P significantly improved the pCR [odds ratio (OR) = 1.33; 95% confidence interval (CI), 1.08-1.63; p = 0.006]. In the metastatic setting, H + P significantly improved PFS [hazard ratios (HRs) = 0.75; 95% CI, 0.68-0.84; p < 0.001]. There was a trend towards better OS but that it did not reach statistical significance (HRs = 0.81; 95% CI, 0.64-1.03; p = 0.082). A subgroup analysis revealed that the HER2+/HR- patients who received H + P showed the highest increase in the pCR. Rash, diarrhea, epistaxis, mucosal inflammation, and anemia were significantly more frequently observed with H + P than with H, whereas myalgia was less frequent (OR = 0.91; 95% CI, 0.82-1.01; p = 0.072), and no significant difference in cardiac toxicity was observed between these therapies (OR = 1.26; 95% CI, 0.81-1.95; P = 0.309).
CONCLUSIONS
Our study confirms that H + P is superior to H in the (neo)adjuvant treatment of HER2+ breast cancer, and increase the risk of acceptable and tolerable toxicity (rash, diarrhea, epistaxis, mucosal inflammation, and anemia).
TRIAL REGISTRATION
A systematic review protocol was registered with PROSPERO (identification number: CRD42018110415 ).
Topics: Ado-Trastuzumab Emtansine; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Docetaxel; Epistaxis; Exanthema; Female; Humans; Molecular Targeted Therapy; Neoadjuvant Therapy; Progression-Free Survival; Receptor, ErbB-2; Trastuzumab
PubMed: 31638935
DOI: 10.1186/s12885-019-6132-0 -
Medicine Sep 2019This study will systematically investigate the efficacy and safety of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for treatment of patients with...
BACKGROUND
This study will systematically investigate the efficacy and safety of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for treatment of patients with HER2-positive breast cancer (HER2-PBC).
METHODS
A comprehensive literature search for this study will consist of 2 parts: electronic database records and gray literature. The electronic database literatures are searched from PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All databases will be searched from inception up to the present. In addition, gray literatures, such as dissertations, ongoing trials, and so on, will also be searched. Two authors will independently read the records, extract data collection, and evaluate the risk of bias. RevMan V.5.3 software will be applied for statistical analysis.
RESULTS
This study will summarize up-to-date evidence of PTD for patients with HER2-PBC via overall survival, complete response, cancer-specific survival, recurrence-free survival, disease-free survival, quality of life, and toxicities.
CONCLUSION
This study will provide efficacy and safety of PTD for HER2-PBC.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Docetaxel; Female; Genes, erbB-2; Humans; Receptor, ErbB-2; Trastuzumab; Treatment Outcome
PubMed: 31568001
DOI: 10.1097/MD.0000000000017262 -
JAMA Cardiology Oct 2019Echocardiographic left ventricular global longitudinal strain (GLS) detects early subclinical ventricular dysfunction and can be used in patients receiving potentially... (Meta-Analysis)
Meta-Analysis
Assessment of Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-analysis.
IMPORTANCE
Echocardiographic left ventricular global longitudinal strain (GLS) detects early subclinical ventricular dysfunction and can be used in patients receiving potentially cardiotoxic chemotherapy. A meta-analysis of the prognostic value of GLS for cancer therapy-related cardiac dysfunction (CTRCD) has not been performed, to our knowledge.
OBJECTIVE
To explore the prognostic value of GLS for the prediction of CTRCD.
DATA SOURCES
Systematic search of the MEDLINE, Embase, Scopus, and the Cochrane Library databases from database inception to June 1, 2018.
STUDY SELECTION
Cohort studies assessing the prognostic or discriminatory performance of GLS before or during chemotherapy for subsequent CTRCD.
DATA EXTRACTION AND SYNTHESIS
Random-effects meta-analysis and hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the prognostic and discriminatory performance of different GLS indices. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity.
MAIN OUTCOMES AND MEASURES
The primary outcome was CTRCD, defined as a clinically significant change in left ventricular ejection fraction with or without new-onset heart failure symptoms.
RESULTS
Analysis included 21 studies comprising 1782 patients with cancer, including breast cancer, hematologic malignancies, or sarcomas, treated with anthracyclines with or without trastuzumab. The incidence of CTRCD ranged from 9.3% to 43.8% over a mean follow-up of 4.2 to 23.0 months (pooled incidence, 21.0%). For active treatment absolute GLS (9 studies), the high-risk cutoff values ranged from -21.0% to -13.8%, with worse GLS associated with a higher CTRCD risk (odds ratio, 12.27; 95% CI, 7.73-19.47; area under the HSROC, 0.86; 95% CI, 0.83-0.89). For relative changes vs a baseline value (9 studies), cutoff values ranged from 2.3% to 15.9%, with a greater decrease linked to a 16-fold higher risk of CTRCD (odds ratio, 15.82; 95% CI, 5.84-42.85; area under the HSROC, 0.86; 95% CI, 0.83-0.89). Both indices showed significant publication bias. Meta-regression identified differences in sample size and CTRCD definition but not GLS cutoff value as significant sources of interstudy heterogeneity.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, measurement of GLS after initiation of potentially cardiotoxic chemotherapy with anthracyclines with or without trastuzumab had good prognostic performance for subsequent CTRCD. However, risk of bias in the original studies, publication bias, and limited data on the incremental value of GLS and its optimal cutoff values highlight the need for larger prospective multicenter studies.
Topics: Antineoplastic Agents; Cardiotoxicity; Early Diagnosis; Echocardiography; Heart Ventricles; Humans; Neoplasms; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 31433450
DOI: 10.1001/jamacardio.2019.2952 -
Expert Review of Clinical Pharmacology Aug 2019: Breast cancer remains to be the globally leading female cancer. About 15% to 20% of breast cancers have human epidermal growth factor receptor 2 (HER2)-positive tumors... (Meta-Analysis)
Meta-Analysis
: Breast cancer remains to be the globally leading female cancer. About 15% to 20% of breast cancers have human epidermal growth factor receptor 2 (HER2)-positive tumors - a more aggressive breast cancer subtype with shortened survival. In the light of new and updated trial data on trastuzumab therapy for HER2-positive early-stage breast cancer (EBC), we conducted a systematic review and meta-analysis to update the pooling of its relative treatment effects. : Systematic search was performed through Pubmed and Scopus to identify studies comparing survival outcomes and risks of heart toxicity effects of adjuvant trastuzumab with chemotherapy versus chemotherapy alone for HER2-positive EBC patients. : Based on the eight included studies in the review, combining trastuzumab with chemotherapy continues to show lowered death and relapse risks by one-third. The decision to initiate trastuzumab, however, needs to be prudently deliberated as two to three times more cardiotoxicity risk was shown to be associated with its use. : Administering adjuvant trastuzumab in a weekly cycle concurrently with anthracycline-taxane chemotherapy regimen appears to be a preferable option to optimize its favorable effect in improving DFS and to prevent significantly higher risk for cardiotoxic effects.
Topics: Antineoplastic Agents, Immunological; Breast Neoplasms; Cardiotoxicity; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Neoplasm Staging; Receptor, ErbB-2; Trastuzumab
PubMed: 31287333
DOI: 10.1080/17512433.2019.1637252