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Revista Portuguesa de Cardiologia :... Dec 2023Breast cancer patients undergoing trastuzumab therapy have greater risk of cardiovascular disease. Risk factors for this effect have been proposed. However, the role of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Breast cancer patients undergoing trastuzumab therapy have greater risk of cardiovascular disease. Risk factors for this effect have been proposed. However, the role of dyslipidemia is not completely understood. This systematic review aimed to explore the role of dyslipidemia in trastuzumab-induced cardiotoxicity.
METHODS
The investigators searched MEDLINE, Scopus, and Web of Science up to October 25, 2020. A random-effects model was used to determine pooled estimates of the results. The primary endpoint was trastuzumab-induced cardiotoxicity in patients with and without dyslipidemia.
RESULTS
A total of 39 studies were selected for inclusion in our systematic review assessing 21079 patients. One study demonstrated a statistically significant association between dyslipidemia and cardiotoxicity (OR=2.28, 95% CI 1.22-4.26, p=0.01). In all other studies, no such association was observed. Twenty-one studies including 6135 patients were eligible for meta-analysis. In this meta-analysis of unadjusted data, dyslipidemia was significantly associated with cardiotoxicity (OR=1.25, 95% CI 1.01-1.53, p=0.04, I=0%), however, a subgroup analysis of studies reporting adjusted measures did not demonstrate a significant association (OR=0.89, 95% CI 0.73-1.10, p=0.28, I=0%).
CONCLUSION
This systematic review and meta-analysis did not demonstrate a significant association between dyslipidemia alone and the development of cardiotoxicity. In the absence of other relevant cardiovascular risk factors, review of lipid profile may not be obligatory, and management of patients could be performed without referral for cardio-oncology assessment. Further investigation of risk factors for trastuzumab-induced cardiotoxicity is required to confirm these results.
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; Cardiotoxicity; Risk Factors; Dyslipidemias
PubMed: 37399885
DOI: 10.1016/j.repc.2022.10.016 -
Cureus May 2023Patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive breast cancer require treatment upfront because of the aggressive nature of this type of... (Review)
Review
Pathologic Complete Response Achieved in Early-Stage HER2-Positive Breast Cancer After Neoadjuvant Therapy With Trastuzumab and Chemotherapy vs. Trastuzumab, Chemotherapy, and Pertuzumab: A Systematic Review and Meta-Analysis of Clinical Trials.
Patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive breast cancer require treatment upfront because of the aggressive nature of this type of cancer. Patients with early-stage HER2-positive breast cancer are usually treated with neoadjuvant therapy. This neoadjuvant therapy comprises targeted therapy and chemotherapy. Targeted therapy is given with trastuzumab. Pertuzumab is either administered or not with trastuzumab as a targeted therapy. This systematic review and meta-analysis aim to find out and compare the benefit achieved in terms of pathologic complete response (pCR) by adding pertuzumab to the neoadjuvant treatment regimen for early-stage HER2-positive breast cancer patients. Various databases were searched to find out relevant clinical trials. After going through PubMed, Embase, and Cochrane, three clinical trials were shortlisted for this systematic review and meta-analysis. These three clinical trials were double-armed. Pertuzumab was present in one arm while being absent in one arm to assess the benefit of adding pertuzumab in terms of pCR achieved. Data were analyzed using RevMan Web (Cochrane, London, UK). The odds ratio and 95% confidence interval were calculated for the outcome. The Mantel-Haenszel method and random effect model were used for analysis. The risk of bias in studies was evaluated using the Cochrane risk of bias tool for randomized controlled trials (ROB2). The summary statistics showed that the incidence of pCR was more in the experimental group (having pertuzumab) as compared to the control group (without pertuzumab) with an odds ratio of 2.10 (95% CI: 1.56-2.83) with I2 = 0%. In three double-arm trials, there were 840 participants, 445 in the experimental group and 395 in the control group. A total of 203 (45%) patients out of 445 in the experimental group achieved pCR, whereas 127 (32%) patients out of 395 in the control group achieved pCR. Through the results of this study, it can be concluded that the rate of pCR achieved was higher in that arm in which pertuzumab was present compared to the study arm in which only trastuzumab was given as targeted therapy. Thus, it can be suggested that pertuzumab be added to the neoadjuvant regimen for early-stage HER2-positive breast cancer patients. This would result in achieving a better pCR. And by improving pCR rates, the survival outcomes of patients can be significantly improved.
PubMed: 37398703
DOI: 10.7759/cureus.39780 -
Archives of Pathology & Laboratory... Sep 2023To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2)...
PURPOSE.—
To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification.
METHODS.—
The Update Panel conducted a systematic literature review to identify signals for updating recommendations.
RESULTS.—
The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations.
RECOMMENDATIONS.—
The 2018 ASCO-CAP recommendations for HER2 testing are affirmed.
DISCUSSION.—
HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines.
Topics: Humans; Female; Breast Neoplasms; In Situ Hybridization, Fluorescence; Receptor, ErbB-2; In Situ Hybridization; Biomarkers, Tumor
PubMed: 37303228
DOI: 10.5858/arpa.2023-0950-SA -
Breast (Edinburgh, Scotland) Jun 2023Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM.
METHODS
We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint.
RESULTS
7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine.
CONCLUSIONS
The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.
Topics: Female; Humans; Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Trastuzumab; Meningeal Neoplasms
PubMed: 37156650
DOI: 10.1016/j.breast.2023.04.008 -
European Journal of Cancer (Oxford,... Sep 2023The recommended preoperative approach for HER2-positive breast cancer is unclear. We aimed to investigate the following: i) what is the optimal neoadjuvant regimen and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The recommended preoperative approach for HER2-positive breast cancer is unclear. We aimed to investigate the following: i) what is the optimal neoadjuvant regimen and ii) whether anthracyclines could be excluded.
METHODS
A systematic literature search in Medline, Embase and Web of Science databases was performed. Studies had to satisfy the following criteria: i) randomised controlled trials (RCTs), ii) enroled patients treated preoperatively for HER2-positive BC (breast cancer), iii) at least one treatment group received an anti-HER2 agent, iv) available information of any efficacy end-point and v) published in English. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. Pathologic complete response (pCR), event-free survival (EFS) and overall survival (OS) were the efficacy end-points of interest, and selected safety end-points were also analysed.
RESULTS
A total of 11,049 patients with HER2-positive BC (46 RCTs) were included in the network meta-analysis, and 32 different regimens were evaluated. Dual anti-HER2-therapy, with pertuzumab or tyrosine kinase inhibitors, combined with chemotherapy was significantly superior to trastuzumab and chemotherapy in terms of pCR, EFS and OS. However, a higher risk of cardiotoxicity was observed with dual anti-HER2-therapy. Anthracycline-based chemotherapy was not associated with better efficacy outcomes in comparison with non-anthracycline-based chemotherapy. In anthracycline-free regimens, the addition of carboplatin presented numerically better efficacy outcomes.
CONCLUSION
Dual HER2 blockade with chemotherapy is the recommended choice as neoadjuvant therapy for HER2-positive breast cancer, preferably by omitting anthracyclines in favour of carboplatin.
Topics: Humans; Female; Neoadjuvant Therapy; Carboplatin; Network Meta-Analysis; Receptor, ErbB-2; Breast Neoplasms; Trastuzumab; Antibiotics, Antineoplastic; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37142539
DOI: 10.1016/j.ejca.2023.03.042 -
Frontiers in Pharmacology 2023Despite the benefits of trastuzumab in many trials, evidence of its impact on health-related quality of life (HRQoL) in early treatment has not been summarized. This...
Despite the benefits of trastuzumab in many trials, evidence of its impact on health-related quality of life (HRQoL) in early treatment has not been summarized. This study explored the effects of trastuzumab treatment on HRQoL, including pooled meta-analysis, in an effort to provide an integrated assessment of HRQoL for Her2-positive early breast cancer patients. A comprehensive literature review to February 2023 using three databases, focusing on treatment using trastuzumab during the early stage, was performed. The mean changes from baseline during and after treatment were extracted from the included randomized control trials (RCTs) papers and total HRQoL scores were obtained from cross-sectional studies included. Mean difference (MD) and 95% confidence intervals were assessed by a random effect or fixed effect model based on heterogeneity (I). A total of ten studies were identified and reviewed, consisting of seven RCTs and three cross-sectional studies. The pooled analysis of the mean change from baseline during treatment resulted in an MD of 1.92 (95% CI = 1.59 to 2.25, < 0.05, I = 0%), favoring the trastuzumab group. A non-significant result of the mean change from baseline after treatment appeared in the analysis of 12-month follow-up. In the cross-sectional studies, pooled analyses of HRQoL showed that trastuzumab meaningfully demonstrated an improved HRQoL profile (MD = 9.29, 95% CI = 1.31 to 17.27, = 0.02, I = 0%). Trastuzumab as a targeted therapy resulted in a favorable effect on HRQoL in the early stages of Her2-positive breast cancer. The findings of significant improvements in patients' HRQoL and less clinically meaningful deterioration in side effects of trastuzumab-containing regimen during treatment were supported by prolonged survival.
PubMed: 37124232
DOI: 10.3389/fphar.2023.1090326 -
ESMO Open Jun 2023Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a distinct subtype with different prognosis and response... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a distinct subtype with different prognosis and response to treatment. HER2-targeted therapy is currently recommended for patients with HR+/HER2+ advanced breast cancer. However, there is debate over which drugs to add on the basis of HER2 blockade yield the optimal efficacy. This systematic review and network meta-analysis was conducted to solve the problem.
METHODS
Eligible randomized controlled trials (RCTs) comparing different interventions in HR+/HER2+ metastatic breast cancer were included. The outcomes of interest included progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Pooled hazard ratios or odds ratios with credible intervals (CrIs) were calculated to estimate the predefined outcomes. The optimal therapeutics were identified by comparing the surface under the cumulative ranking curves (SUCRA).
RESULTS
Totally, 23 literatures of 20 RCTs were included. Regarding PFS, significant differences were detected between single or dual HER2 blockade plus endocrine therapy (ET) versus ET alone and dual HER2 blockade plus ET versus physician's choice. Trastuzumab, pertuzumab plus chemotherapy significantly improved PFS than trastuzumab plus chemotherapy (hazard ratio 0.69, 95% CrI 0.50-0.92). The SUCRA values suggested the relatively better efficacy of dual HER2-targeted therapy plus ET (86%-91%) than chemotherapy (62%-81%) in prolonging PFS and OS. The HER2 blockade-containing regimens showed similar safety profiles in eight documented TRAEs.
CONCLUSIONS
Prominent status of dual-targeted therapy for patients with HR+/HER2+ metastatic breast cancer was revealed. Compared with chemotherapy-containing regimens, the ET-containing ones showed better efficacy and similar safety profiles, which could be recommended in clinical practice.
Topics: Humans; Female; Network Meta-Analysis; Receptor, ErbB-2; Breast Neoplasms; Trastuzumab; Progression-Free Survival
PubMed: 37084609
DOI: 10.1016/j.esmoop.2023.101216 -
Annals of Translational Medicine Mar 2023Neoadjuvant therapy has become the standard treatment for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer, with most regimens using a...
BACKGROUND
Neoadjuvant therapy has become the standard treatment for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer, with most regimens using a combination of anti-HER2-targeted drugs and chemotherapy. However, the combination of anthracyclines and trastuzumab has high cardiac toxicity, and the efficacy evaluation of targeted therapy with or without anthracyclines is not unified. The purpose of this meta-analysis was to evaluate the relative efficacy and safety of anti-HER2-targeted therapy combined with . without anthracyclines neoadjuvant treatment.
METHODS
The following databases: PubMed, Medline, Embase, and Cochrane Library were systematically searched. Study inclusion was determined according to PICOS principles. PICOS: Patients, HER2-positive breast cancer; Intervention, anti-HER2-targeted therapy combined with anthracyclines; Control, without anthracyclines; Outcomes, the percentage of pathologic complete response (pCR), breast-conserving surgery (BCS), and grade 3 or worse adverse events according to CTCAE version 4.03; Studies, randomized controlled trials (RCTs) and retrospective studies. The meta-analysis was performed using RevMan5.3 software, and the odds ratio (OR) with 95% confidence intervals (CIs) was performed.
RESULTS
In total, 11 articles involving 1,998 patients were included with 1,155 patients in the anthracycline-containing group and 843 patients in the anthracycline-free group. For efficacy, there was no statistically significant difference in the percentage of pCR (OR 0.95; 95% CI: 0.61-1.48; P=0.83) and BCS (OR 1.18; 95% CI: 0.93-1.49; P=0.17) on anthracycline-free regimens compared with anthracycline-containing regimens. For safety, the combined effect values showed a significantly lower incidence of left ventricular ejection fraction decreases with the anthracycline-free regimen than with the anthracycline-containing regimen (OR 0.50; 95% CI: 0.35-0.71; P=0.0001). Other adverse effects and survival events were generally not statistically different in incidence between the two groups. The subgroup analysis suggested that hormone receptor status might be the source of heterogeneity in this study.
CONCLUSIONS
Our study demonstrated that the targeted therapy combined with anthracyclines was associated with an increased risk of cardiac adverse events compared with the anthracycline-free group, with no significant difference in the percentage of pCR and BCS. Due to the high heterogeneity of this meta-analysis, more studies with longer follow-up are needed to validate the current findings and to further explore the removal and retention of anthracyclines.
PubMed: 37007556
DOI: 10.21037/atm-22-4030 -
Frontiers in Oncology 2023Many options for third-line treatment of advanced gastric cancer (GC) or gastroesophageal junction carcinoma (GEJC) have been developed. Therapies including...
BACKGROUND
Many options for third-line treatment of advanced gastric cancer (GC) or gastroesophageal junction carcinoma (GEJC) have been developed. Therapies including immunotherapy (nivolumab), chemotherapy (irinotecan, FTD/TPI), targeted therapy (apatinib), and antibody drug conjugates (ADC) have shown to increase the survival rates in patients, but few studies have compared the relative efficacy of these treatments. Here, we compared the efficacies of these regimens using network meta-analysis (NMA) to provide guides in selecting the best regimen and formulating a precise individualized treatment plan.
METHODS
The published RCTs of phase II/III in PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched. The median overall survival (mOS) was the primary outcome of NMA, and the other outcomes were median progression-free survival (mPFS), disease control rate (DCR) (proportion of patients with confirmed CR, PR, or stable disease (SD)) and incidence of grade 3 or above adverse events (≥3AEs).
RESULTS
Five phase II/III RCTs involving 1674 patients and 7 treatment regimens were analyzed. It showed that Trastuzumab Deruxtecan (DS-8201) prolonged the OS of patients significantly comparing with chemotherapy (HR: 0.59; 95% CI: 0.39-0.89) for the overall population. DS-8201 (HR: 0.27; 95% CI: 0.17-0.42) and chemotherapy (HR: 0.57; 95% CI: 0.47-0.7) improved the PFS significantly over nivolumab. Apatinib (RR: 3.04; 95% CI: 1.65-5.95) and DS-8201 (RR: 2.67; 95% CI: 1.51-4.83) were more effective than nivolumab in improving DCR. DS-8201 achieved greater OS benefits compared to chemotherapy (HR: 0.59; 95% CI: 0.39-0.88) for patients who were HER2-positive. We ranked the Bayesian surface under the cumulative ranking curve according to OS benefit, and showed that ADC ranked first for the general patient population and for patients with a HER2-positive diagnosis, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. For patients with GEJC, nivolumab ranked first.
CONCLUSIONS
Nivolumab, apatinib, chemotherapy, and ADC all improved the OS of GC/GEJC patients significantly. ADC may be the best option for the overall population of GC, as well as for patients with HER2-overexpression, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. Nivolumab may be the first treatment option for GEJC patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022364714.
PubMed: 36937403
DOI: 10.3389/fonc.2023.1118820 -
Translational Cancer Research Feb 2023Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients continue to progress despite multiple anti-HER2-targeted treatments. A number...
BACKGROUND
Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients continue to progress despite multiple anti-HER2-targeted treatments. A number of studies have found that Pyrotinib, a small-molecule pan-ErbB receptor tyrosine kinase inhibitor (TKI), is effective in treating patients with HER2-positive metastatic breast cancer. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Pyrotinib in the treatment of HER2-positive metastatic breast cancer.
METHODS
PubMed, Embase, Web of Science, and Cochrane Library databases were searched until February 2022. Research on HER2-positive metastatic breast cancer being treated with Pyrotinib in any line of therapy was included, both prospective and retrospective. Statistical pooling and meta-analysis of data from the included studies were performed to explore the efficacy and safety of Pyrotinib in HER2-positive metastatic breast cancer.
RESULTS
In this meta-analysis, 23 studies were included. The overall objective response rate was 0.49 (95% CI: 0.40, 0.58) for Pyrotinib in HER2-positive metastatic breast cancer and 0.52 (95% CI: 0.32, 0.71) in those with brain metastases. The objective response rate of Pyrotinib was superior to that of other second-line therapeutics in comparison (RR =1.38, 95% CI: 1.25, 1.52), but was relatively inferior to trastuzumab emtansine (T-DM1) (RR =0.82, 95% CI: 0.36, 1.85). The combined median progression-free survivals (PFSs) for Pyrotinib in metastatic breast cancer and those with brain metastases were 8.2 (95% CI: 6.8, 9.5) months and 8.9 (95% CI: 6.2, 11.7) months, respectively. The most common adverse reaction was diarrhea with an all-grade incidence of 0.84 (95% CI: 0.74, 0.92), followed by nausea and vomiting of 0.52 (95% CI: 0.36, 0.68).
CONCLUSIONS
In any line of treatment for HER2-positive metastatic breast cancer, the Pyrotinib-containing regimens demonstrated considerable tumor response, disease control, and survival with manageable adverse effects.
PubMed: 36915587
DOI: 10.21037/tcr-22-1746