Background and Objectives: This meta-analysis compared the efficacy and safety of peramivir compared to other neuraminidase inhibitors (NAIs). Materials and Methods: Data from PubMed, Embase, and Cochrane databases and ClinicalTrials.gov were searched until January 2019. Randomized controlled trials (RCTs) and observational studies (OSs) comparing peramivir with other NAIs for treating influenza were included. The Grading of Recommendations, Assessments, Development, and Evaluations (GRADE) system was used to judge the overall certainty of evidence; the result was moderate. The primary outcome was time to alleviation of symptoms. Twelve articles involving 2681 patients were included in this meta-analysis. We used a random-effect model to pool the effect size, which is expressed as the difference in means (MD), risk ratio (RR), and 95% confidence interval (CI). Results: Overall, peramivir was superior to other NAIs (MD = −11.214 hours, 95% CI: −19.119 to −3.310). The incidence of adverse events (RR = 1.023, 95% CI: 0.717 to 1.460) and serious adverse events (RR = 1.068, 95% CI: 0.702 to 1.625) in the peramivir group was similar to those in the oseltamivir group. In addition, peramivir had higher efficacy than each NAI alone. Conclusion: In conclusion, the efficacy of peramivir might be higher than that of other NAIs, and this agent is tolerated as well as other NAIs.

Acute myeloid leukemia (AML) is one of the most frequent forms of acute leukemia and the second most common leukemia subtype in adults. In 2020, the incidence of AML in the United States was estimated to be ~4 cases per 100,000 adults. The FMS‑like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutation are major prognostic indicators of AML. They are more frequently observed in younger AML patients (aged <60 years), likely due to their association with de novo. Additionally, these mutations have a stronger negative impact on survival in younger patients. Therefore, quizartinib and gilteritinib are second‑generation FLT3 inhibitors that are frequently applied for treating patients with AML. However, to the best of our knowledge, few studies have compared the efficacy of second‑generation FLT3 inhibitors for AML treatment. Therefore, the present study conducted a comprehensive search for studies on the efficacy and safety of FLT3 inhibitors across PubMed, Embase, the Cochrane Library and ClinicalTrials.gov. The search criteria were limited to randomized controlled trials (RCTs). Subsequently, a meta‑analysis was performed on a total of five randomized controlled trials, involving 1,543 participants in total, using a random‑effects model. In each RCT, compared to the salvage chemotherapy used in the control group, the groups that received second‑generation FLT3 inhibitors experienced significant improvements in overall survival (hazard ratio, 0.717; 95% CI, 0.604‑0.850; P<0.001). In addition, overall survival was found to be consistent across the different types of second‑generation FLT3 inhibitors used and different types of AML. The risks associated with a prolonged heart‑rate corrected QT interval (QTc) interval were next evaluated. Compared with the salvage chemotherapy used in the control group, the second‑generation FLT3 inhibitor group exhibited a significantly higher risk of having a prolonged QTc interval (odds ratio, 6.311; 95% CI, 3.061‑13.013; P<0.001). In conclusion, these findings suggest that second‑generation FLT3 inhibitors can improve the overall survival of patients with AML. However, QTc prolongation is a potential adverse effect that should be monitored.

Venetoclax, an orally administered B‑cell lymphoma 2 inhibitor, requires dose adjustments when coadministered with cytochrome P450 inhibitors in patients with acute myeloid leukemia (AML). The present study retrospectively analyzed data on progression‑free survival (PFS), overall survival (OS) and drug‑related adverse events in patients with AML who received adjusted low‑dose venetoclax with antifungal agents, compared with those receiving conventional chemotherapy regimens (I3A7, LDAC, and I2A5) , at a single hospital. In total, 45 patients with AML who were treated between January 2015 and December 2021 were retrospectively included. A significantly longer median OS time was observed in the group receiving idarubicin [12 mg/m² intravenous (IV) on days 1‑3] and cytarabine (100 mg/m² continuous IV infusion on days 1‑7) (I3A7 group) (median not reached) compared with that in the venetoclax group [10.7 months; 95% confidence interval (CI), 6.3‑20.8], the low‑dose cytarabine (LDAC) group (4.7 months; 95% CI, 0.8‑18.7) and the group receiving idarubicin (12 mg/m² IV on days 1‑2) with cytarabine (100 mg/m² continuous IV infusion on days 1‑5) (I2A5 group) (2.3 months; 95% CI, 0.5‑2.3). Similarly, the median PFS time was significantly longer in the I3A7 group (29.0 months; 95% CI, 1.1‑29.0) compared with that in the venetoclax (8.0 months; 95% CI, 0.8‑10.8), LDAC (2.1 months; 95% CI, 0.1‑6.4) and I2A5 (0.9 months; 95% CI, 0.1‑4.7) groups. Grade 3 or higher adverse hematological events were common across all treatment groups. Cardiovascular events and grade 3 or higher tumor lysis syndrome occurred only in the venetoclax group (14 and 7%, respectively). In conclusion, low‑dose venetoclax combined with antifungal agents appears to be less effective than standard treatment but superior to both LDAC and the I2A5 treatment regimens. Venetoclax also demonstrates a relatively low infection risk. However, careful monitoring for cardiovascular events and tumor lysis syndrome during venetoclax administration is crucial, particularly in patients with relevant medical histories.

Breast cancer is the most common malignancy, with approximately ∼20% of cases involving HER2 overexpression. Trastuzumab deruxtecan (T-DXd), an HER2-targeted antibody-drug conjugate, is approved for HER2-high and HER2-low disease. This meta-analysis assessed four randomized controlled trials (DESTINY-Breast02, -03, -04, and -06; 2555 patients) from PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. A random-effects model revealed that T-DXd significantly improved progression-free survival (hazard ratio [HR] = 0.433; 95% confidence interval [CI]: 0.305-0.616; P < 0.001; I² = 90.7%) and overall survival (HR = 0.720; 95% CI: 0.636-0.816; P < 0.001; I² = 0%) versus control regimens, with consistent benefits across HER2 subgroups. However, T-DXd increased the risks of interstitial lung disease (relative risk [RR] = 13.832; P < 0.001), decreased left ventricular ejection fraction (RR = 2.247; P < 0.001), anemia, nausea, vomiting, decreased appetite, and alopecia; neutropenia and diarrhea risks were comparable between groups. These findings highlight T-DXd's survival benefits and toxicity profile warranting monitoring.

Venetoclax, an oral B-cell lymphoma-2 (BCL-2) inhibitor, shows promise in cancer treatment but has an unclear safety profile. This meta-analysis evaluates the safety of venetoclax, focusing on adverse events. Data from PubMed, Embase, Cochrane databases, and ClinicalTrials.gov were retrieved up to August 2023. Nine studies were included based on specific inclusion and exclusion criteria. A random effects model was used to calculate risk ratios (RRs) and 95% confidence intervals (CIs). The meta-analysis included nine studies. Venetoclax was associated with increased risks of neutropenia (RR = 1.427, 95% CI = 1.118 to 1.822), diarrhea (RR = 1.889, 95% CI = 1.388 to 2.570), and cardiovascular events (RR = 1.726, 95% CI = 1.088 to 2.737). However, the risk of tumor lysis syndrome (TLS) with venetoclax was not increased compared to the comparators (RR = 1.478, 95% CI = 0.504 to 4.337). Venetoclax increases the risk of hematological, gastrointestinal, and cardiac adverse events. Clinicians should monitor these side effects, especially in patients with preexisting conditions. Further research is needed to fully understand venetoclax's safety profile. https://inplasy.com/ identifier is INPLASY2023110041.

INPLASY202570096 Efficacy and Safety of Trastuzumab Deruxtecan in HER2-High and HER2-Low Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Keywords: Trastuzumab d…