The efficacy of anakinra compared to standard care of treatment for COVID-19: a meta-analysis.

BACKGROUND: As SARS-CoV-2 continues to spread worldwide, this study brings to light the link that anakinra, a recombinant IL-1 receptor antagonist, has in averting grave clinical outcomes. The objectives of this meta-analysis are to investigate the effects of anakinra in interventional groups compared to control/standard of care groups on mortality along with the provision of a prevalence estimate of the variables associated with death (C-reactive protein-CRP, ferritin, acute respiratory distress syndrome-ARDS). METHODS: According to the PRISMA 2020 statement guidelines, a systematic search was conducted from December 19, 2020, until December 10, 2021, with keywords including COVID-19, coronavirus, SARS-CoV-2, anakinra, mortality, across the following databases: PubMed/MEDLINE, Scopus, Web of Science, CINAHL Plus, and Cochrane. A random-effects model was applied using RevMan 5.4 for all statistical analyses. RESULTS: The meta-analysis pooled in 1297 participants with 565 (43.6%) patients in the anakinra group. When comparing to the control/standard of care group, the anakinra group had a much lower risk of death (RR = 0.47. 95% CI = 0.37-0.59, Z = 6.44; P < 0.001). In addition to the risk of death being reduced by around 50% in the interventional group, prognostic indicators such as CRP and ferritin were improved with fewer occurrences of severe ARDS. DISCUSSION: Patients with COVID-19 pneumonia may be treated with anakinra as a safe and viable treatment modality to defer adverse outcomes such as a death in the 28-day period. Despite an auspicious premise, our findings must be used with caution as adequately powered randomized, placebo-controlled trials are required to corroborate these findings.

Atezolizumab and pembrolizumab in triple-negative breast cancer: a meta-analysis.

BACKGROUND: The approval of anti-PD-L1 drugs, including atezolizumab/pembrolizumab in triple-negative breast cancer (TNBC), potentially improveme treatment regimens available for TNBC. METHODS: We conducted a meta-analysis to review the efficacy of atezolizumab/pembrolizumab for the treatment of TNBC in both the adjuvant and neoadjuvant settings. We calculated standardized mean difference (SMD) for the associations of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) to estimate objective response rate (ORR) and pathological complete response (pCR), using 95% confidence intervals (CIs). RESULTS: Six clinical trials comprising 3612 patients were included. For adjuvant therapies, the ORR (OR = 1.26, P = 0.04) of atezolizumab/pembrolizumab plus chemotherapy was higher in the intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (d = 1.55, P < 0.001). The atezolizumab plus chemotherapy group had a positive effect size for OS compared to control groups (d = 0.52, P < 0.001). In the neoadjuvant setting, patients in ITT arms had higher pCR rates than the control groups (OR = 1.61, P = 0.001). CONCLUSION: We collate evidence of atezolizumab/pembrolizumab as viable therapeutics among patients with TNBC with PD-L1 subgroups deriving higher benefits.

PLAIN LANGUAGE SUMMARYImmune checkpoint inhibitors (ICI), atezolizumab and pembrolizumab, have received approval for patients with triple-negative breast cancer (TNBC) expressing PD-L1. Thus far, it has only been approved for patients with unresectable locally advanced or metastatic TNBC. With the IMpassion 130 and KEYNOTE-355 trials introducing the immunotherapy era for TNBC, ongoing trials have started exploring the outcomes of the ICIs in early-stage TNBC in combination. Recently, the ICIs have demonstrated positive efficacy outcomes in neoadjuvant settings. Both the ICIs have shown a safe profile in terms of adverse events. The recent advances made by clinical trials indicate promising results for early-stage and advanced/metastatic TNBC. However, there is a need to harmonize and explore biomarkers and endpoints in the ongoing clinical trials to enhance patient treatment protocols. As TNBC is an aggressive subtype, exploring beyond the PD-L1 positive subgroup is necessary to expand the target population receiving ICIs for TNBC.