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Cancer Treatment Reviews Apr 2023There is an increasing need for developing effective therapies for managing intracranial disease in patients with human epidermal growth factor receptor 2-positive (HER2... (Review)
Review
Epidemiology, clinical outcomes, and unmet needs of patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases: A systematic literature review.
BACKGROUND
There is an increasing need for developing effective therapies for managing intracranial disease in patients with human epidermal growth factor receptor 2-positive (HER2 +) metastatic breast cancer and brain metastases (BM), as this population is growing and has historically been excluded from large clinical trials. In this systematic literature review, we aimed to provide a comprehensive overview of the epidemiology, unmet needs, and global treatment landscape for patients with HER2 + metastatic breast cancer and BM, with a particular focus on heterogeneity across clinical trial designs in this setting.
METHODS
We conducted literature searches of PubMed and select congress websites up to March 2022 and filtered for publications with a significant focus on epidemiology, unmet needs, or treatment outcomes in patients with HER2 + metastatic breast cancer and BM.
RESULTS
Key clinical trials of HER2-targeting treatments for HER2 + metastatic breast cancer had varying eligibility criteria relating to BM, with only two trials-HER2CLIMB and DEBBRAH-including patients with both active and stable BM. We also observed variance across assessed central nervous system (CNS)-focused endpoints (CNS objective response rate vs CNS progression-free survival vs time to CNS progression) and robustness of statistical analysis (prespecified vs exploratory).
CONCLUSIONS
There is an unmet need for standardization of clinical trial design for patients with HER2 + metastatic breast cancer and BM, to aid the interpretation of the global treatment landscape and ensure patients with all types of BM can access effective treatments.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Receptor, ErbB-2; Brain Neoplasms
PubMed: 36893691
DOI: 10.1016/j.ctrv.2023.102527 -
Frontiers in Oncology 2023Many systemic treatment options are available for patients with human epidermal growth factor 2 (HER2)-positive breast cancer brain metastases. However, it is unclear...
INTRODUCTION
Many systemic treatment options are available for patients with human epidermal growth factor 2 (HER2)-positive breast cancer brain metastases. However, it is unclear which pharmacological treatment option is the most beneficial.
METHODS
We searched databases, such as PubMed, Embase, and Cochrane Library, and conference abstracts according to keywords. We extracted progression-free survival (PFS), overall survival (OS) data, and overall response rate (ORR) from randomized controlled trials and single-arm studies of HER2-positive breast cancer brain metastasis treatment for meta-analysis and analyzed different drug-related adverse events (AEs).
RESULTS
Three randomized controlled trials and seven single-arm clinical studies with 731 patients with HER2-positive brain metastases from breast cancer involving at least seven drugs were included. In randomized controlled trials, our results showed that trastuzumab deruxtecan significantly improved PFS and OS in patients and was superior to other drug regimens. In the single-arm study, the ORR was more pronounced for the trastuzumab deruxtecan and pyrotinib plus capecitabine regimens (ORR, 73.33%; 95% confidence intervals [CI], 44.90%-92.21%; ORR, 74.58%; 95% CI, 61.56%-85.02%, respectively). We found that the main AEs of antibody-drug conjugate (ADC) were nausea and fatigue, while the main AE of small-molecule tyrosine kinase inhibitor (TKI) drugs and large monoclonal antibodies was diarrhea.
CONCLUSIONS
Trastuzumab deruxtecan was shown to be the most significant in improving survival in patients with HER2-positive breast cancer brain metastases in network meta-analysis, and in single-arm study, patients with HER2-positive breast cancer brain metastases treated with trastuzumab deruxtecan and pyrotinib plus capecitabine regimen had the highest ORR. The main AEs associated with ADC, large monoclonal antibodies, and TKI drugs were nausea, fatigue, and diarrhea, respectively.
PubMed: 36890831
DOI: 10.3389/fonc.2023.1003565 -
Critical Reviews in Oncology/hematology Apr 2023The benefit of adjuvant trastuzumab treatment in patients with HER2-positive breast tumors ≤ 10 mm without lymph node involvement (T1abN0) is insufficiently... (Meta-Analysis)
Meta-Analysis Review
The benefit of adjuvant trastuzumab treatment in patients with HER2-positive breast tumors ≤ 10 mm without lymph node involvement (T1abN0) is insufficiently investigated. The aim of this systematic review and meta-analysis was to examine if adjuvant trastuzumab improves the prognosis in these patients. Databases were searched to identify interventional and observational studies evaluating the effect of trastuzumab on breast cancer specific survival (BCSS), disease free survival (DFS), distant recurrence free survival (DRFS), overall survival (OS) or recurrence free survival (RFS). Twelve studies examining the effect of trastuzumab and nine control studies without trastuzumab were identified (n = 6927). Median follow-up was 36-123 months. Significantly improved DFS (Hazard Ratio (HR) 0.14, p < 0.0001) and OS (HR 0.17, p = 0.011) were found for patients receiving trastuzumab and chemotherapy compared to no trastuzumab/chemotherapy based on four and two studies. The prognosis was good even for patients without trastuzumab treatment: 5-year DFS 88.3% and 5-year OS 95.9%.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Breast Neoplasms; Prognosis; Disease-Free Survival; Adjuvants, Immunologic; Chemotherapy, Adjuvant
PubMed: 36854373
DOI: 10.1016/j.critrevonc.2023.103952 -
EClinicalMedicine Jan 2023Given the increasing use of HER2-targeted antibody-drug conjugates (ADCs) worldwide, the summary of toxicity incidence and profiles of these drugs is crucial to provide...
BACKGROUND
Given the increasing use of HER2-targeted antibody-drug conjugates (ADCs) worldwide, the summary of toxicity incidence and profiles of these drugs is crucial to provide reference for clinical application. This meta-analysis aimed to estimate the mean incidences of treatment-related adverse events of HER2-targeted ADCs and to investigate the differences between different drugs and cancer types.
METHODS
We performed a systematic search of literature in PubMed, Embase, Web of Science, and Scopus databases from inception to February 1, 2022 and the last search was updated to August 1, 2022. Published prospective clinical trials on single-agent of the US Food and Drug Administration approved HER2-targeted ADCs with available count data regarding treatment-related adverse events were included. The primary outcomes were pooled incidences of treatment-related adverse events and differences between different drugs and cancer types. The data synthesis was performed using a Bayesian hierarchical modelling method and the protocol was registered in PROSPERO (CRD42022331627).
FINDINGS
A total of 39 studies (37 trials) involving 7688 patients across five cancer types were included in the final analysis. On pooling the data using Bayesian hierarchical modelling, the overall mean incidence of all-grade adverse events, high-grade adverse events, serious adverse events, and adverse events that resulted in drug discontinuation were 98.29% (95% CrI, 97.33%-99.07%, τ = 1.49), 47.88% (95% CrI, 42.74%-53.17%, τ = 0.37), 19.45% (95% CrI, 15.70%-23.67%, τ = 0.55), and 10.52% (95% CrI, 8.03%-13.21%, τ = 0.56), respectively. The most common all-grade adverse events were nausea (41.57%; 95% CrI, 40.46%-42.64%, τ = 0.81), fatigue (35.86%; 95% CrI, 34.85%-36.96%, τ = 0.65), and decreased appetite (28.84%; 95% CrI, 22.93%-36.87%, τ = 0.76). The most common high-grade adverse events were thrombocytopenia (8.37%; 95% CrI, 7.75%-9.07%, τ = 0.71), anaemia (6.49%; 95% CrI, 5.86%-7.11%, τ = 1.06), and neutropenia (6.42%; 95% CrI, 5.76%-7.04%, τ = 1.21). We found no difference in the mean incidences of adverse events among different cancer types, as well as different dosing regimens. However, trastuzumab deruxtecan (T-DXd) appeared to have higher mean incidences of adverse events compared with trastuzumab emtansine (T-DM1), especially for the higher dose of T-DXd (6.4 mg/kg Q3W).
INTERPRETATION
The incidences of adverse events between two HER2-targeted ADCs were similar in different cancer types, but different HER2-targeted ADCs appeared to have different mean incidences of adverse events. The comprehensive summary of the adverse events of HER2-targeted ADCs is critical for clinicians caring for patients with cancer receiving HER2-targeted ADCs therapy.
FUNDING
The National Natural Science Foundation of China (Grant No. 82073402) and Key R&D Plan of Hubei Province, China (No.2020BCA060) funded this study.
PubMed: 36712893
DOI: 10.1016/j.eclinm.2022.101795 -
Cancers Jan 2023Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of... (Review)
Review
BACKGROUND
Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of cardiac function over time, in the absence of cardioprotection, which less is known about.
METHODS
This PRISMA-guideline-adherent review was registered on PROSPERO (CRD42022373496).
RESULTS
26 studies met the eligibility criteria including a total of 910 patients. The overall reduction in post-anthracycline pooled mean left ventricular ejection fraction (LVEF) in placebo arms of the included randomised-controlled trials was 4.5% (95% CI, 2.6 to 6.4). The trend in LVEF showed a progressive decline until approximately 180 days, after which there was no significant change. Those receiving a cumulative anthracycline dose of 300 mg/m2 experienced a more profound reduction. The overall pooled risk of a 10% absolute decline in LVEF from baseline, or a decline to an LVEF below 50%, was 17% (95% CI: 11 to 24; I2 = 71%). Sensitivity analyses of baseline LVEF and trastuzumab treatment status did not yield significant differences.
CONCLUSION
While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines is required.
PubMed: 36672461
DOI: 10.3390/cancers15020512 -
PloS One 2023It is critical to select subsequent treatments for patients after the failure of trastuzumab therapy. Following the failure of standard trastuzumab therapy guidelines in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
It is critical to select subsequent treatments for patients after the failure of trastuzumab therapy. Following the failure of standard trastuzumab therapy guidelines in the Chinese Society of Clinical Oncology, pyrotinib and capecitabine is a grade I recommended regimen for treating patients with HER2-positive metastatic breast cancer. Concurrently, in treating patients with HER2-positive metastatic breast cancer, lapatinib and capecitabine are also recommended regimens for those who have previously received taxanes, anthracyclines, and trastuzumab therapy. However, there is currently no systematic review and meta-analysis comparing pyrotinib with lapatinib among HER2+ MBC patients. Therefore, this study aims to perform a systematic review and meta-analysis and assess whether pyrotinib is superior to lapatinib in efficacy and safety.
METHODS
Relevant trials were searched in CNKI, Wanfang, VIP, PubMed, Embase, and Cochrane CENTRAL databases from inception until March 27th, 2022. The primary outcomes were PFS and OS, and the secondary outcomes were ORR and grade ≥3 AEs.
RESULTS
Five relevant studies were included in this study, including 2 RCTs and 3 retrospective cohort studies. Pyrotinib combined with chemotherapy is superior to lapatinib combined with chemotherapy among HER2+ metastatic breast cancer patients, with a significant improvement in PFS (prior trastuzumab therapy) (HR: 0.47, 95% CI: 0.39-0.57, p<0.001, I2 = 0%, FEM), PFS (trastuzumab resistance) (HR: 0.52, 95% CI: 0.39-0.68, p<0.001, I2 = 40%, FEM) and ORR (RR: 1.45, 95% CI: 1.26-1.67, p<0.001, I2 = 8%, FEM), but has higher grade ≥3 diarrhea incidence (RR: 2.68, 95% CI: 1.85-3.90, p<0.001, I2 = 44%, FEM).
CONCLUSIONS
The efficacy of pyrotinib combined with chemotherapy is superior to lapatinib combined with chemotherapy but has more safety risks.
Topics: Humans; Female; Breast Neoplasms; Lapatinib; Capecitabine; Retrospective Studies; Receptor, ErbB-2; Trastuzumab; Treatment Failure; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36602979
DOI: 10.1371/journal.pone.0279775 -
Journal of Pharmaceutical Policy and... Dec 2022Breast cancer (BC) is the most common cancer globally among women, with 2,261,419 new cases in 2020; systemic treatment may be neo-adjuvant, adjuvant, or both. BC... (Review)
Review
BACKGROUND
Breast cancer (BC) is the most common cancer globally among women, with 2,261,419 new cases in 2020; systemic treatment may be neo-adjuvant, adjuvant, or both. BC subtype guides the standard systemic therapy administered, which consists of endocrine therapy for all HR + tumors, trastuzumab-based HER2-directed antibody therapy plus chemotherapy for all HER2 + tumors (with endocrine therapy given in addition, if concurrent HR positivity), and chemotherapy alone for the triple-negative subtype. This study aimed to identify, evaluate, and systematically review all budget impact analyses (BIAs) of BC medications worldwide.
METHODS
PubMed, Scopus, and Web of Science Core Collection databases were thoroughly searched up to 26th March 2022 to identify original published studies which evaluate BIA of BC medications. ISPOR Task Force guidelines were used to assess the quality of included studies. This study was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
In total, 17 BIAs were included in the study. About half of the studies were conducted in Europe. The results of the BIAs showed that most of the included BIAs are conducted from the payer's perspective; they have different methodological frameworks for recommended chemotherapy, targeted therapy, and immunotherapy agents to treat BC. For the same medications, the results of budgetary effects are not consistent in diverse countries. Nine out of the 17 studies were focused on trastuzumab, in which the biosimilar form reduced costs, but the brand form increased costs, especially in a 52-week treatment period.
CONCLUSION
Researchers should conduct the budget impact analysis of high-value medications such as anti-tumor drugs more objectively, and the accuracy of parameters needs to be more strictly guaranteed. Furthermore, it is worthy of declaring that the budgetary impact of the same drug is not always consistent over time, so the researchers should measure access to medication in the long run.
PubMed: 36581921
DOI: 10.1186/s40545-022-00493-1 -
Systematic Reviews Dec 2022Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from lapatinib and lapatinib plus trastuzumab therapy than standard trastuzumab therapy. This study presents an update of a systematic review and meta-analysis involving comparison of lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy.
AIM
We determined whether trastuzumab plus lapatinib or lapatinib therapy is not inferior to trastuzumab therapy in HER2-positive breast cancer patients.
METHODS
Relevant trials were searched in CNKI, Wanfang, VIP, Sinomed, PubMed, Embase, and Cochrane CENTRAL databases from inception until October 25, 2021. Primary outcomes were OS, DFS/EFS, and PFS while secondary outcomes were pCR (ypT0/is ypN0), pCR (ypT0/is ypN0/+), ORR, DCR, rate of BCS, RFS, cardiac toxicities, and other toxicities.
RESULTS
Thirteen randomized controlled trials were included in this study. Trastuzumab combined with lapatinib therapy was found to be superior to standard trastuzumab therapy alone with regard to overall survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0), pathologic complete response (ypT0/is ypN0/+), recurrence-free survival, higher incidences of diarrhea, and rash/skin toxicity. Lapatinib therapy was established to be inferior to trastuzumab therapy in overall survival, progression-free survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0) and pathologic complete response (ypT0/is ypN0/+), diarrhea, and rash/skin toxicity and had a low incidence of left ventricular ejection fraction decline.
CONCLUSIONS
The efficacy of trastuzumab combined with lapatinib therapy is superior to standard trastuzumab therapy alone; however, it has more non-cardiac grade III/IV toxicities. Moreover, the efficacy of lapatinib therapy is inferior to that of standard trastuzumab therapy alone.
Topics: Humans; Female; Trastuzumab; Lapatinib; Breast Neoplasms; Receptor, ErbB-2; Stroke Volume; Antineoplastic Combined Chemotherapy Protocols; Ventricular Function, Left; Randomized Controlled Trials as Topic
PubMed: 36496473
DOI: 10.1186/s13643-022-02134-9 -
International Journal of Health Sciences 2022The objective of the study was to assess the incidence of chemotherapy cardiotoxicity. (Review)
Review
OBJECTIVE
The objective of the study was to assess the incidence of chemotherapy cardiotoxicity.
METHODS
This is a systematic review carried out through the PubMed, VHL and Scientific Electronic Library Online databases, using the descriptors "Cardiotoxicity" and "Chemotherapy" associated with the Boolean operator "AND." Initially, 15,090 articles were found between 2015 and 2021. After applying the defined inclusion and exclusion criteria, 80 studies remained, of which 27 underwent complete reading, after which all were included in the study.
RESULTS
In total, 32,009 cancer patients were analyzed, of which 27,270 (85.2%) were female. Breast cancer was the most frequent neoplasm, with 11,145 (34.8%) cases. Regarding the type of chemotherapy, anthracycline was the most prevalent, analyzed in 18 (66.7%) studies, followed by trastuzumab, in 9 (33.3%) studies. Of the studies evaluated, five did not present any case of cardiotoxicity, a total of 2255 (8.3%) cases were recorded, in addition other outcomes mentioned in patients after chemotherapy were arrhythmia ( = 522), acute coronary syndrome ( = 185), diastolic dysfunction ( = 184), cardiomyopathy ( = 161), and arterial hypertension ( = 89).
CONCLUSION
Post-chemotherapeutic cardiotoxicity was mentioned in most studies, being present in a relevant percentage of the sample. Furthermore, these patients may develop other cardiovascular events.
PubMed: 36475028
DOI: No ID Found -
PloS One 2022Trastuzumab is a valuable therapy option for women with ERBB2(HER2)+ breast cancer tumours, often used in combination with chemotherapy and alongside other therapies. It... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab is a valuable therapy option for women with ERBB2(HER2)+ breast cancer tumours, often used in combination with chemotherapy and alongside other therapies. It is known to have adverse effects, but these have proved difficult to separate from the effects of other concurrent therapies patients are usually taking. This study aims to assess the adverse effects specifically attributable to trastuzumab, and whether they vary by patient subgroup or concurrent therapies.
METHODS
As registered on PROSPERO (CRD42019146541), we used previous systematic reviews as well as the clinicaltrials.gov registry to identify randomised controlled trials in breast cancer which compared treatment regimes with and without trastuzumab. Neoadjuvant, adjuvant and metastatic settings were examined. Data was extracted from those which had, as of July 2022, reported adverse events. Risk of bias was assessed using ROB2. Primary outcomes were adverse events of any type or severity (excluding death). A standard random-effects meta-analysis was performed for each outcome independently. In order to ascertain whether adverse effects differed by individual factors such as age or tumour characteristics, or by use of trastuzumab concurrently with hormone therapy, we examined individual-level patient data for one large trial, HERA.
RESULTS
79 relevant trials were found, of which 20 contained comparable arms of trastuzumab-containing therapy and corresponding matched therapy without trastuzumab. This allowed a comparison of 8669 patients receiving trastuzumab versus 9556 receiving no trastuzumab, which gave a list of 25 statistically and clinically significant adverse effects related to trastuzumab alone: unspecified pain, asthenia, nasopharyngitis, skin disorders (mainly rash), dyspepsia, paraesthesia, infections (often respiratory), increased lacrimation, diarrhoea, myalgia, oedema (limb/peripheral), fever, nose bleeds, cardiac events, insomnia, cough, back pain, dyspnoea, chills, dizziness or vertigo, hypertension, congestive heart failure, increased levels of aspartate aminotransferase, gastrointestinal issues and dehydration. Analysis of individual patient-level data from 5102 patients suggested that nausea is slightly more likely for women taking trastuzumab who are ER+ /also taking hormone therapy than for those who are ER-/not taking hormone therapy; no other potential treatment-subgroup interactions were detected. We found no evidence for significantly increased rates of neutropenia, anaemia or lymphopenia in patients on trastuzumab-containing regimes compared to those on comparable regimes without trastuzumab.
CONCLUSIONS
This meta-analysis should allow clinicians and patients to better identify and quantify the potential adverse effects of adding trastuzumab to their treatment regime for breast cancer, and hence inform their decision-making. However, limitations include serious risk of bias due to heterogeneity in reporting of the outcomes and the open-label nature of the trials.
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Neutropenia; Hormones
PubMed: 36454979
DOI: 10.1371/journal.pone.0275321