The decreased left ventricular ejection fraction in patients using trastuzumab deruxtecan for her2-positive breast cancer: a systematic review and meta-analysis

Breast Cancer (BC) is one of the most common cancers diagnosed in population femmale and it has several subtypes, one of them being theexpressing human epidermal growth factor receptor 2 positive (HER2 +), one of the treatments for HER2+ breast cancer consists of chemotherapy plus trastuzumab deruxtecan. Several clinical trials have shown the effectiveness and safety of trastuzumabe deruxtecano in cancer patients, however, several Adverse Events (AEs) have been described and the decrease in left ventricular ejection has been singled out for more prominent analysis. Objective: We conducted a systematic review and meta-analysis to investigate the cardiovascular effects of Trastuzumab Deruxtecano and whether it can influence the appearance of reduced left ventricular ejection fraction.. METHODS: We performed a systematic search in Embase, PubMed and Cochrane databases for randomized controlled trials (RCTs) showed a decrease in left ventricular ejection fraction in patients using trastuzumab deruxtecan against Her-2-positive breast cancer compared to patients to used another's treatments against this disease. Mean difference (MD) with 95% confidence intervals (CI) were calculated using a random effects model. The heterogeneity was examined in the I2 statistic. P-values > 0.05 were considered statistically significant. The statistical analysis was carried out using R software version 4.2.3. RESULTS: A total of 3 RCTs were included, with a total of 1656 patients evaluated, 928 patients randomized to the use of Trastuzumab Deruxtecan and 728 patients to the use of other treatments according to medical choice, follow-up ranged from 10 to 38 months. There was a visible in the decrease in left ventricular ejection fraction, with a higher incidence in the group that used trastuzumab compared to the placebo group (RR: 5.73%; 95% CI 1.51 - 21.78; I2 33% ; P= 0.010466). Another important point is the discontinuation of treatment due to grade 2 adverse events, classified as reduced LVEF, where a higher incidence is seen in the group that used Trastuzumab Deruxtecan compared to the placebo group (RR 2.11%; 95% CI 1.54 - 2.89; P = 0.000003),7. CONCLUSION: In this meta-analysis, Trastuzumab Deruxtecan showed a relationship with a decrease in left ventricular ejection fraction, displaying the need for more studies to evaluate the cardiotoxicity of trastuzumab and its effects as a whole on the cardiovascular system.

Omitting Axillary Lymph Node Dissection Is Associated With an Increased Risk of Regional Recurrence in Early Stage Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Breast cancer (BC) is a global problem, however, despite ALND is considered the standard treatment for early stage BC with node-positive, there is no sufficient data to determine which of these patients should undergo it. Thus, the aim of this systematic review was to clarify if there is any difference between NALND and ALND in terms of safety and prognosis of the patients. A shearch was carried in PubMed, Embase and Cochrane databases for studies that compared NALND and ALND. The statistics was performed in R software, in which fixed and random effect models were employed for outcomes with, respectively, I² < 25% and I² > 25%, to compute risk ratios and hazard ratios with 95% CI. Heterogeneity was accessed with I2 statistics. There was 9 included studies, involving 11,543patients, of whom 5831 were randomized to omission of ALND. The follow-up period ranged from 5 to 15 years, with participant ages varying from 53.4 to 70.1 years. The analysis revealed significant increase in regional recurrence at the end of the follow-up (RR 1.73; 95% CI, 1.13 to 2.66) and a significant decrease in lymphedema (RR 0.35; 95% CI, 0.24 to 0.52), however no significant result was found for OS (HR 1.01; 95% CI, 0.89 to 1.15). Our data suggest that while the NALND offers benefits in terms of preventing lymphedema, it was associated with a higher risk of of regional recurrences. Thus, further studies are necessary to fully assess the role of these techniques in BC management.

Safety and efficacy of moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: a meta-analysis

BACKGROUND Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide and poses a significant healthcare related challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear. METHODS A thorough literature study was conducted across PubMed, Embase, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients. RESULTS In the 13 included studies, involving 8,592 patients, 4,525 (52.67%) of which received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 4 to 156 weeks, with participant ages varying LDL-C from 55.2 to 71 years old. Analysis revealed significant MIS+EZT-associated with greater percentages of patients achieved the goal in Low-Density Lipoprotein (LDL-C) < 70 (Odds Ratio (OR) 1.76; 95% CI [1.26; 2.45]; p=0.001; I²=73%), LDL-C reduction (Mean Difference (MD) -5.05 mg/dL; 95% CI [-9.02;-1.07]; p<0.013; I²=56%;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95% CI [-14.90; -0.91]; p<0.027; I²=60%); Triglycerides reduction (MD -8.20 mg/ dL; 95% CI [-13.05; -3.35]; p<0.001; I²=2%;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95% CI [0.79; 1.78]; p=0.404; I²=0%); and Drug intolerance (RR 0.78; 95% CI [0.32; 1.92]; p=0.584; I²=35%). CONCLUSIONS This meta-analysis highlights the effectiveness of MIS+EZT in improving significant lipid profile components for ASCVD patients, as can been seen through the greater percentage of patients achieving the LDL-C <70 mg/dL target and lower LDL-C, total cholesterol and triglycerides levels. Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.

Efficacy and Safety of Anti-CD38 Monoclonal Antibodies in Patients with Relapsed or Refractory Multiple Myeloma: A Meta-Analysis of Randomized Clinical Trials.

The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progression-free survival (HR 0.52; 95% CI 0.43-0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63-0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26-1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02-1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38-2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13-1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms.

Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed or refractory multiple myeloma: a meta-analysis of randomized clinical trials

The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progressionfree survival (HR 0.52; 95% CI 0.43­0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63­0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26­1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02­1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38­2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13­1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms.