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Frontiers in Cardiovascular Medicine 2021Several cardiovascular risk factors have been suggested to be associated with anthracycline-induced cardiotoxicity, but their quantitative effects have not reached a...
Several cardiovascular risk factors have been suggested to be associated with anthracycline-induced cardiotoxicity, but their quantitative effects have not reached a consensus. We searched PubMed, EMBASE, and Cochrane Library databases for manuscripts published from inception to February 2021, which reported the results of cardiotoxicity due to anthracycline chemotherapy without trastuzumab. Cardiotoxicity defined by any reduction of left ventricular eject fraction (LVEF) to below 50% or a >10% reduction from baseline was defined as the primary endpoint. Odd ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model meta-analysis. A total of 7,488 patients receiving anthracycline chemotherapy without trastuzumab were included, who had at least one risk factor at baseline. Hypertension (OR: 1.99; 95% CI: 1.43-2.76), diabetes mellitus (OR: 1.74; 95% CI: 1.11-2.74), and obesity (OR: 1.72; 95% CI: 1.13-2.61) were associated with increased risk of cardiotoxicity. In addition, the relative reduction of global longitudinal strain (GLS) from baseline after anthracycline treatment could significantly improve the detection ability of cardiotoxicity (28.5%, 95% CI: 22.1-35.8% vs. 16.4%, 95% CI: 13.4-19.9%) compared with LVEF. The early detection rate of anthracycline-induced cardiotoxicity (3 months after chemotherapy) by GLS was 30.2% (95% CI: 24.9-36.1%), which is similar with the overall result of GLS. Hypertension, diabetes mellitus, and obesity are associated with increased risk of anthracycline-induced cardiotoxicity, which indicates that corresponding protective strategies should be used during and after anthracycline treatment. The findings of higher detection rate and better early detection ability for cardiotoxicity than LVEF added new proofs for the advantages of GLS in detection of AIC.
PubMed: 34660739
DOI: 10.3389/fcvm.2021.736854 -
European Review For Medical and... Sep 2021Although bevacizumab and trastuzumab have been widely added to the standard regimen for metastatic breast cancer, the clinical outcomes remain controversial. The purpose... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Although bevacizumab and trastuzumab have been widely added to the standard regimen for metastatic breast cancer, the clinical outcomes remain controversial. The purpose of this study was to conduct meta-analysis to verify the clinical efficacy and safety of docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer (MBC).
MATERIALS AND METHODS
All available literature of clinical trials about docetaxel, bevacizumab, trastuzumab and metastatic breast cancer was pooled from PubMed, Embase and Cochrane library database. The meta-analysis combined the progression free survival (PFS), overall response rate (ORR) and incidence of all grades adverse events in MBC patients.
RESULTS
Seven clinical trials were included by two reviewers. Docetaxel and bevacizumab with trastuzumab show the pooled PFS was 16.53 months (95% CI: 13.95-19.11 months), the pooled ORR was 0.75 (95% CI: 0.69-0.80) in HER2-positive MBC patients. Docetaxel and bevacizumab show that the pooled PFS was 8.49 months (95% CI: 7.80-9.18 months), the pooled ORR was 0.51(95% CI: 0.47-0.55) in HER2-negative MBC patients.
CONCLUSIONS
Both for patients with HER2-positive and negative metastatic breast cancer, docetaxel and bevacizumab with or without trastuzumab as first-line treatment resulted in long survival, especially in terms of progression-free survival. Although the overall response rates are also significantly improved, it is still controversial based on the current evidence.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Docetaxel; Female; Humans; Progression-Free Survival; Receptor, ErbB-2; Survival Rate; Trastuzumab
PubMed: 34533811
DOI: 10.26355/eurrev_202109_26643 -
Cancer Causes & Control : CCC Dec 2021
PubMed: 34533664
DOI: 10.1007/s10552-021-01495-1 -
Frontiers in Oncology 2021The presence of anti-HER2 agents, such as trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1), significantly improved the prognosis of metastatic HER2-positive...
BACKGROUND
The presence of anti-HER2 agents, such as trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1), significantly improved the prognosis of metastatic HER2-positive (HER2+) breast cancers (BC). However, drug resistance and disease progression are still common. In order to further improve the treatment efficacy, new clinical trials about anti-HER2 agents in combination with chemotherapy are growing rapidly. We conducted the network meta-analysis to synthesize evidences of clinical trials to identify the best therapy for metastatic HER2+ BC.
METHODS
A systematic search of randomized controlled trials regarding anti-HER2 agents in combination with chemotherapy for advanced or metastatic breast cancers up to May 2020 was conducted in Embase, PubMed, and the Cochrane Library. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR), and safety. Bayesian network meta-analysis was conducted to synthesize the results and rank the therapies.
RESULTS
Twenty-six studies, including 16 studies for first-line treatments and 10 studies for second- or later-line treatments were included in the network meta-analysis. For first-line studies, the THP (taxanes + trastuzumab + pertuzumab) regimen exhibited the highest probability to be the optimal treatment in all efficacy outcomes and moderate safety. For second- or later-line studies, the T-DM1 and XHTuC (capecitabine + trastuzumab + tucatinib) regimens ranked top two in all efficacy outcomes according to the surface under the cumulative ranking (SUCRA) results. T-DM1 ranked first in PFS and OS whereas XHTuC ranked first in ORR. The safety outcomes of T-DM1 and XHTuC were acceptable.
CONCLUSIONS
THP was still the optimal first-line treatment for metastatic HER2+ BC. T-DM1 and XHTuC were recommended for second-line treatments.
SYSTEMATIC REVIEW REGISTRATION
INPLASY.com, identifier (INPLASY202090086).
PubMed: 34490125
DOI: 10.3389/fonc.2021.731210 -
Annals of Translational Medicine Jul 2021Trastuzumab emtansine (T-DM1) has been proved to have value and efficacy in the treatment of advanced metastatic cancer, including in the adjuvant setting. However,...
BACKGROUND
Trastuzumab emtansine (T-DM1) has been proved to have value and efficacy in the treatment of advanced metastatic cancer, including in the adjuvant setting. However, there is increasing concern about T-DM1-induced thrombocytopenia (TCP), which shows racial differences in incidence. This meta-analysis aimed to evaluate differences in the incidence of T-DM1-related TCP between Asian and non-Asian patients by combining accessible information from all single-agent T-DM1 clinical trials published to date.
METHODS
We conducted systematic searches of the PubMed, Embase, and the Cochrane Library databases to identify relevant clinical studies of T-DM1 that reported on safety, including the incidence of TCP, which were published between January 1980 and March 2020. Two reviewers were responsible for the screening and extraction of data. The pooled-effect estimate calculated with a fixed-effects or random-effects model was represented as incidence with 95% confidence intervals (CIs).
RESULTS
A total of 29 studies involving 6,188 patients were included. The incidence of all-grade TCP in Asian patients and non-Asian patients was 0.39 (95% CI: 0.11-0.67) and 0.29 (95% CI: 0.23-0.35), respectively. The incidence of TCP of grade 3 or higher in Asians was 0.20 (95% CI: 0.10-0.29), compared with 0.02 (95% CI: 0.01-0.03) in non-Asians. Gastrointestinal cancer type and a T-DM1 treatment dose of 2.4 mg/kg Q3W were related to grade 3 or higher TCP events.
DISCUSSION
Asian patients have a higher risk of developing TCP after receiving T-DM1 than non-Asian patients. Clinicians should be aware of the importance of careful observation of platelet count in patients receiving T-DM1 therapy.
PubMed: 34430580
DOI: 10.21037/atm-21-2763 -
Cancer Causes & Control : CCC Dec 2021Cardiotoxicity affects 5-16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We... (Meta-Analysis)
Meta-Analysis
PURPOSE
Cardiotoxicity affects 5-16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies.
METHODS
A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran's Q test and the I test.
RESULTS
Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27-0.78), p = 0.004, [Formula: see text] = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17-1.45), p = 0.20, [Formula: see text] = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75-9.52), p < 0.001, [Formula: see text] = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82-11.68, p = 0.024, [Formula: see text] = 80.9%]. We were unable to explore publication bias due to the small number of studies.
CONCLUSION
This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab.
TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION
PROSPERO: CRD42020140352 on 7/6/2020.
Topics: Anthracyclines; Cardiotoxicity; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neoplasms; Trastuzumab
PubMed: 34406595
DOI: 10.1007/s10552-021-01487-1 -
Frontiers in Oncology 2021This meta-analysis aimed to better elucidate the predictive value of human epidermal growth factor receptor 2 (HER2)-enriched subtype of pathological complete response...
BACKGROUND
This meta-analysis aimed to better elucidate the predictive value of human epidermal growth factor receptor 2 (HER2)-enriched subtype of pathological complete response (pCR) rate within HER2-positive breast cancer patients receiving neoadjuvant treatment.
METHODS
We identified prospective trials that evaluated the correlation between an HER2-enriched subtype and pCR rate in HER2-positive breast cancer. Pooled odds ratio (OR) values with 95% confidence intervals (CIs) were computed.
RESULTS
Fifteen studies comprising 2,190 patients met the inclusion criteria. The HER2-enriched subtype was associated with increased odds of achieving a pCR (OR = 4.12, 95% CI = 3.38 to 5.03, < 0.001) in patients overall. Moreover, it was correlated with improved pCR when single or dual HER2-targeted agent-based therapy was employed (OR = 3.36, 95% CI = 2.25 to 5.02, < 0.001; OR = 4.66, 95% CI = 3.56 to 6.10, < 0.001, respectively), but not when HER2-targeted agent-free chemotherapy was used (OR = 2.52, 95% CI = 0.98 to 6.49, P = 0.05). Moreover, an HER2-enriched subtype predicted higher pCR rates irrespective of HER2-targeted agents (trastuzumab, lapatinib, pertuzumab, or T-DM1); chemotherapy agents (taxane-based, or anthracyclines plus taxane-based); endocrine therapy and hormone receptor [all the differences were statistically significant ( all ≤ 0.001)].
CONCLUSIONS
The HER2-enriched subtype can more effectively and specifically predict pCR for HER2-targeted agent-based neoadjuvant treatment, irrespective of the number (single or dual) or category of HER2-targeted agent, including chemotherapy and endocrine therapy, or hormone receptor in cases of HER2-positive breast cancer.
PubMed: 34367947
DOI: 10.3389/fonc.2021.632357 -
The Oncologist Oct 2021Platinum and fluoropyrimidine combinations typically comprise first-line (1L) therapy in advanced gastric cancer or gastroesophageal junction adenocarcinoma (G/GEA),...
BACKGROUND
Platinum and fluoropyrimidine combinations typically comprise first-line (1L) therapy in advanced gastric cancer or gastroesophageal junction adenocarcinoma (G/GEA), although controversy exists regarding the use of 5doublet versus triplet cytotoxic regimens. Historically, second-line (2L) and third-line or later (3L+) therapy has been fragmented. Recent trials have increased the need for optimal treatment sequencing in advanced G/GEA.
MATERIALS AND METHODS
We conducted a systematic search of peer-reviewed manuscripts of randomized clinical trials examining 1L, 2L, and 3L+ therapy for advanced G/GEA published from 2009 through November 19, 2019. When available, overall survival, progression-free survival, time to progression, overall response rate, and toxicity were extracted from each and compared descriptively.
RESULTS
In 1L therapy, chemotherapy triplets demonstrated variable efficacy improvements with invariable increased toxicity compared with platinum/fluoropyrimidine doublets. Currently, the only published report of positive outcomes using biologics in 1L describes adding trastuzumab in HER2-overexpressing advanced G/GEA. In 2L, doublet chemotherapy regimens are not uniformly more efficacious than single-agent taxanes or irinotecan, and ramucirumab has demonstrated improved outcomes both as monotherapy and in combination.
CONCLUSION
For advanced G/GEA, review of trial results from 2009-2019 support 1L therapy with platinum and fluoropyrimidine and sequencing with taxanes or irinotecan in combination with biologics as effective 2L options. Escalating to a triplet may add some efficacy at the expense of added toxicity.
IMPLICATIONS FOR PRACTICE
The rapidly changing treatment landscape for advanced gastric cancer includes increasing options for refractory disease. With multiple first-line platinum-based regimens, identification of those with the best benefit-to-risk ratio may provide guidance on treatment sequencing strategies. This article presents findings from the published literature of randomized controlled trials that included a first-line platinum/fluoropyrimidine combination and, for second-line trials, patients with platinum/fluoropyrimidine-refractory disease. This guiding summary could be a tool for clinicians to identify the optimal first-line regimen(s) followed by a strategy for subsequent regimens.
Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Esophageal Neoplasms; Esophagogastric Junction; Humans; Stomach Neoplasms
PubMed: 34288262
DOI: 10.1002/onco.13907 -
Cureus May 2021Background Peripheral neuropathy (PN), especially peripheral sensory neuropathy (PSN), is significant toxicity of taxanes, the most used class of microtubule inhibitors...
Relative Risk of Peripheral Neuropathy With Ado-Trastuzumab Emtansine (T-DM1) Compared to Taxane-Based Regimens in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Cancers: A Systematic Review and Meta-Analysis.
Background Peripheral neuropathy (PN), especially peripheral sensory neuropathy (PSN), is significant toxicity of taxanes, the most used class of microtubule inhibitors for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. Ado-trastuzumab emtansine (T-DM1) is a HER2-targeted antibody-drug conjugate, consisting of trastuzumab and a microtubule inhibitor DM1, which has been approved for HER2-positive breast cancer. T-DM1 has also been found to cause significant PN, including PSN. Methods We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials using T-DM1 in the experimental arm and a taxane-based regimen in the control arm to determine the relative risk of PN and PSN associated with T-DM1 as compared to taxanes. A total of 1,857 patients were included in the analysis. The Cochran-Mantel-Haenszel method and the random-effects model were used to calculate the pooled risk ratio (RR) with a 95% confidence interval (CI) for all-grade and grade ≥3 PN and PSN. Results The relative risks of all-grade PN and all-grade PSN were lower with T-DM1 compared to taxanes. The pooled RR of all-grade PN was 0.59, 95% CI: 0.39-0.89, P = 0.01, and the pooled RR of all-grade PSN was 0.58, 95% CI: 0.46-0.74, P < 0.0001. Conclusions Our meta-analysis demonstrated that T-DM1 is associated with a relatively lower risk of all-grade PN and PSN than the taxane-based regimens for HER2-positive cancers. It could be an area of consideration in selecting therapy for HER2-positive breast cancer patients at high risk of developing or having pre-existing PN and PSN.
PubMed: 34194883
DOI: 10.7759/cureus.15282 -
Frontiers in Oncology 2021Breast cancer is one of the most frequent cancer types worldwide and the first cause of cancer-related deaths in women. Although significant therapeutic advances have...
Breast cancer is one of the most frequent cancer types worldwide and the first cause of cancer-related deaths in women. Although significant therapeutic advances have been achieved with drugs such as tamoxifen and trastuzumab, breast cancer still caused 627,000 deaths in 2018. Since cancer is a multifactorial disease, it has become necessary to develop new molecular therapies that can target several relevant cellular processes at once. Ion channels are versatile regulators of several physiological- and pathophysiological-related mechanisms, including cancer-relevant processes such as tumor progression, apoptosis inhibition, proliferation, migration, invasion, and chemoresistance. Ion channels are the main regulators of cellular functions, conducting ions selectively through a pore-forming structure located in the plasma membrane, protein-protein interactions one of their main regulatory mechanisms. Among the different ion channel families, the Transient Receptor Potential (TRP) family stands out in the context of breast cancer since several members have been proposed as prognostic markers in this pathology. However, only a few approaches exist to block their specific activity during tumoral progress. In this article, we describe several TRP channels that have been involved in breast cancer progress with a particular focus on their binding partners that have also been described as drivers of breast cancer progression. Here, we propose disrupting these interactions as attractive and potential new therapeutic targets for treating this neoplastic disease.
PubMed: 34178620
DOI: 10.3389/fonc.2021.621614