Background Triple-Negative Breast Cancer (TNBC) is a lethal subtype of breast cancer with limited treatment options. The purpose of this Network Meta-Analysis (NMA) is to compare the efficacy and safety of inhibitors of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in treating TNBC. Methods Our search strategy was used in six databases: PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature database, Embase, Scopus, and Web of Science up to November 2nd, 2022, as well as a thorough search in the most used trial registries. We included phase II and III randomized controlled trials that looked at the efficacy of PD-1/PD-L1 inhibitors in the treatment of TNBC and reported either Overall Survival (OS), Progression-Free Survival (PFS), or pathological Complete Response (pCR). The risk of bias was assessed utilizing Cochrane's risk of bias 2 tool, and the statistical analysis was performed using a frequentist contrast-based method for NMA by employing standard pairwise meta-analysis applying random effects model. Results 12 trials (5324 patients) were included in our NMA including seven phase III trials. Pembrolizumab in a neoadjuvant setting achieved a pooled OS of 0.82 (95% Confidence Interval (CI) 0.65 to 1.03), a PFS of 0.82 (95% CI 0.71 to 0.94) and a pCR 2.79 (95% CI 1.07 to 7.24) compared to Atezolizumab’s OS of 0.92 (95% CI 0.74 to 1.15), PFS of 0.82 (95% CI 0.69 to 0.97), and pCR of 1.94 (95% CI 0.86 to 4.37). Atezolizumab had less grade ≥ 3 adverse events (OR 1.48, 95% CI 0.90 to 2.42) than Pembrolizumab (OR 1.90, 95% CI 1.08 to 3.33) in the neoadjuvant setting. Conclusions PD-1/PD-L1 inhibitors exhibited varying efficacy in terms of OS, PFS, and pCR. They were associated with an increase in immune-related adverse effects. When used early in the course of TNBC, PD-1/PD-L1 inhibitors exert their maximum benefit. Durvalumab as a maintenance treatment instead of chemotherapy has shown promising outcomes. Future studies should focus on PD-L1 expression status and TNBC subtypes, since these factors may contribute to the design of individualized TNBC therapy regimens. Systematic review registration PROSPERO Identifier: CRD42022380712.
SummaryBackgroundSeveral studies have compared the performance of reverse transcription-polymerase chain reaction (RT-PCR) and antigen rapid diagnostic tests (Ag-RDTs) as tools to diagnose SARS-CoV-2 disease (COVID-19). As the performance of Ag-RDT may vary among different products and viral load scenarios, the clinical utility of the Ag-RDT remains unclear. Our aim is to assess the diagnostic agreement between Ag-RDTs and RT-PCR in testing for COVID-19 across different products and cycle threshold (Ct) values.MethodsAn evidence synthesis and meta-analysis of Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) was conducted after an exhaustive search of five databases to locate published studies that compared Ag-RDT to RT-PCR and reported quantitative comparison results. After the screening, quality assessment, and data extraction, the synthesis of pooled estimates was carried out utilizing the quality-effects (QE) model and Freeman-Tukey double arcsine transformation (FTT) for variance stabilization. Subgroup analysis was also conducted to evaluate the tests’ diagnostic agreement across distinctive products and Ct-value thresholds.FindingsA total of 420 studies were screened by title and abstract, of which 39 were eventually included in the analysis. The overall NPA was 99.4% (95%CI 98.8-99.8, I2=91.40%). The PPA was higher in lower Ct groups such as groups with Ct <20 and Ct <25, which had an overall PPA of 95.9% (95%CI 92.7-98.2, I2=0%) and 96.8% (95%CI 95.2-98.0, I2=50.1%) respectively. This is in contrast to groups with higher Ct values, which had relatively lower PPA. Panbio and Roche Ag-RDTs had the best consistent overall PPA across different Ct groups especially in groups with Ct <20 and Ct <25.InterpretationThe findings of our meta-analysis support the use of Ag-RDTs in lieu of RT-PCR for decision making regarding COVID-19 control measures, since the enhanced capacity of RT-PCR to detect disease in those that are Ag-RDT negative will be unlikely to have much public health utility. This step will drastically reduce the cost and time in testing for COVID-19.FundingThis research did not receive any specific funding.
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