ABSTRACT
OBJECTIVES: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis, integrating data from the latest clinical trials, aimed to evaluate the safety and efficacy of T-DXd in this patient population. METHODS: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd's efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data. RESULTS: Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR=0.37, 95% CI: 0.27-0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR=2.10, 95% CI: 1.36-3.25), fatigue (OR=1.56, 95% CI: 1.21-2.02), nausea (OR=6.42, 95% CI: 4.37-9.42), vomiting (OR=6.21, 95% CI: 3.14-12.25), constipation (OR=2.26, 95% CI: 1.53-3.34), and notably, drug-related interstitial lung disease (OR=10.89, 95% CI: 3.81-31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis. CONCLUSIONS: T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles.
ABSTRACT
OBJECTIVES: Breast cancer is the most diagnosed cancer in women, with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) being the predominant subtype. Sacituzumab govitecan (SG), a novel antibody-drug conjugate, has emerged as a promising treatment for metastatic HR+/HER2- breast cancer. This systematic review and meta-analysis aimed to evaluate its efficacy and safety. METHODS: Adhering to "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines, a comprehensive search was conducted in PubMed, Scopus, and Cochrane databases up to December 2023. We included clinical trials and observational studies evaluating SG in patients with HR+/HER2- advanced breast cancer. The primary outcome was progression-free survival (PFS). In contrast, the secondary outcomes included overall survival, objective response rate, clinical benefit rate, duration of response (DOR), and adverse event profiles. Review Manager (Version 5.4) was used for the statistical analysis. RESULTS: Nine studies met the inclusion criteria for systematic review; 2 were suitable for meta-analysis. The pooled analysis showed a hazard ratio of 0.53 (95% CI: 0.34-0.83; P= 0.005; I2 = 86%) for PFSl and a hazard ratio of 0.63 (95% CI: 0.36-1.11; P= 0.11; I2 = 92%) for overall survival. The pooled analysis of the duration of response showed significant results with a standard mean difference = 0.22 (95% CI: 0.03-0.42; P = 0.02; I2 = 61%). CONCLUSION: SG demonstrates significant benefit in PFS and duration of response in patients of HR+/HER2- advanced breast cancer.
ABSTRACT
Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for various hematological malignancies. Still, its remarkable efficacy is accompanied by unique adverse events that must be carefully managed. This comprehensive literature review evaluates the safety profile of CAR T-cell therapy, focusing on cytopenia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), and other potential complications. Cytopenia, characterized by reduced blood cell counts, affects a significant proportion of patients, with rates of anemia, neutropenia, and thrombocytopenia reaching up to 60%, 70%, and 80%, respectively. Risk factors include high tumor burden, prior chemotherapy, and bone marrow involvement. Cytokine release syndrome (CRS) occurs in 13% to 77% of patients and is linked to the cytokine storm induced by CAR T cells, target antigen expression, and preexisting immune dysregulation. Other notable adverse events discussed are cytokine release syndrome, neurotoxicity, and infections. Understanding the mechanisms, risk factors, and management strategies for these adverse events is crucial for optimizing patient outcomes and unlocking the full potential of this revolutionary therapy. The review highlights the need for continued research, interdisciplinary collaboration, and evidence-based approaches to enhance the safety and efficacy of CAR T-cell therapy.
ABSTRACT
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe immunologic disorder that can be fatal if left untreated. The condition is characterized by excessive immune system activation and is often triggered by infections such as Epstein-Barr virus (EBV). Rituximab, an anti-CD20 monoclonal antibody, has been suggested as a treatment, particularly for EBV-associated HLH. METHODS: A systematic review was conducted using PRISMA guidelines, with a literature search spanning PubMed, Scopus, Web of Science, and the Cochrane Library. The inclusion criteria focused on studies that assessed rituximab's efficacy in treating HLH. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. RESULTS: Of 783 identified records, 24 studies were included in the final analysis. Rituximab was typically administered at 375 mg/m2, with varying doses and treatment frequency. Clinical response, often seen within 1 month, was assessed by improvements in clinical symptoms and laboratory findings. Survival rates posttreatment displayed a wide range, with instances of complete remission and disease-free periods, as well as reports of relapse and mortality. CONCLUSION: Rituximab demonstrates the potential for significant clinical benefit in treating HLH, particularly when associated with EBV, showing promise in reducing disease activity and contributing to remission. These findings encourage further research and clinical trials to refine the therapeutic protocols and better understand the long-term effects of rituximab in HLH management.
ABSTRACT
Breast cancer is the second leading cause of women's cancer deaths after lung cancer. Risk factors such as environment, lifestyle, and genetics contribute to its development, including mutation in the breast cancer (BRCA) gene. Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) target these mutations, benefiting patients with advanced cancers. This review summarizes PARPi' safety and efficacy in the treatment of BRCA-mutated breast cancer. PubMed, The Cochrane Library for Clinical Trials, and Science Direct, were searched for articles from inception to April 2024. Eligible articles were analyzed, and data were extracted for meta-analysis using RevMan 5.4 software with a random-effect model. Out of 430 articles identified from online databases, only 6 randomized control trials including 3610 patients were included in the analysis. PARPi therapy improved progression-free survival (hazard ratio: 0.64; 95% CI: 0.56, 0.73; P< 0.00001) and overall survival (hazard ratio: 0.84; 95% CI: 0.73, 0.98 P = 0.02), according to the analysis. In our safety analysis, the risk of adverse events was not statistically different between PARPi versus chemotherapy (relative risk [RR]: 1.08; 95% CI: 0.44, 2.68; P = 0.86), and combined PARPi and standard chemotherapy (RR: 1.00; 95% CI: 0.93, 1.07; P = 0.80). The only statistically significant difference was observed in anemia, where PARPi increased the risk of developing anemia compared with standard chemotherapy (RR: 6.17; 95% CI: 2.44, 15.58; P = 0.0001). In BRCA-mutated breast cancer, PARPi treatment shows better overall survival and progression-free survival compared with standard chemotherapy or placebo. Furthermore, PARPi, either alone or in combination therapy, does not increase the risk of adverse events in these patients, as per the meta-analysis.
