These data, along with other real-world studies 12, support the role of Pt in the first-line salvage chemotherapy for mTNBC. A latest meta-analysis of randomized controlled clinical trials (RCTs) from Cochrane library in 2020 indicated that Pt-containing regimens might improve time to progression or progression-free survival (TTP/PFS) of metastatic TNBC (mTNBC) patients, and provide a small benefit to overall survival (OS) 11. Since TNBC has been reported to harbor more proportion (>50%) of homologous DNA recombination defects, either due to BRCA mutation or other mechanisms, it’s supposed that TNBC might be more sensitive to Pt agents 8, 9, 10. Thus platinum is believed to be specially active in those cancer cells with DNA repair deficiency.
Platinum can cause DNA strand breaks, consequently leading to cell apoptosis 7. Platinum (Pt) agents, usually referring to carboplatin (Cb) and cisplatin(DDP), are cytotoxic DNA-damaging chemo-drugs widely used in various malignancies. However, even with the assistance of dose-dense regimens and guidance of NACT, the improvement of long-term survival is still critical for eTNBC. Adjuvant addition of capecitabine for those TNBC patients with non-pCR (pathological complete response) after standard NACT has been recommended in most guidelines 6. Moreover, neoadjuvant chemotherapy (NACT) has also provided more information in tailoring subsequent treatments for BC patients. In the past decade, dose-dense regimens have been proved to be more effective in adjuvant treatments of high-risk BC patients 4, 5. To date, anthracyclines (A/E) and taxanes(T) based chemo-regimens, administrated in various combinations and schedules, have been widely accepted as the standard regimens for early stage TNBC (eTNBC) 2, 3. Due to insensitivity to endocrine therapy and anti-HER2 therapy, chemotherapy is the dominant systemic treatment for TNBC in general. Triple negative breast cancer (TNBC), i.e., ER (estrogen receptor)-, PR (progesterone receptor)-, and HER-2 (human epithelial growth factor receptor-2)-, accounting for 15−20% in breast cancer, is a highly aggressive subtype with a significantly inferior prognosis than non-TNBC 1. Based on efficiency and toxicity, we recommend Pt-based regimens for eTNBC, especially the “A&T + Pt” mode if the toxicities are tolerable, which may lead TNBC therapy into a new era. The present meta-analysis of RCTs revealed that Pt-based chemo-regimens could significantly improve both DFS and OS for eTNBC patients. The survival benefits also remained consistent in either neoadjuvant or adjuvant use of Pt. The survival benefits of DFS remained consistent in both the two strategies of Pt usage, either adding Pt to standard anthracyclines&taxanes based regimens (A&T + Pt), or combination of Pt and taxanes alone (TPt). Seven eligible RCTs enrolling a total of 2,027 eTNBC patients were identified in this meta-analysis, with 1,007 receiving Pt-free regimens, and the other 1,020 patients receiving Pt-based regimens, respectively. We extracted the survival data and utilized the STATA software to calculate the summarized hazard ratios (HRs) and 95% confidence interval (95% CI) for overall survival (OS) and disease-free survival (DFS). We carried out a comprehensive literature search on 15 March 2021 for randomized controlled trials (RCTs) comparing ajuvant/neoadjuvant Pt-based and Pt-free chemo-regimens in eTNBC patients, according to PRISMA 2020. We conducted a meta-analysis to explore its role in improving the clinical outcomes of eTNBC. However, the survival benefit of Pt-based regimens in early stage TNBC(eTNBC) treatment has remained unclear.
Platinum (Pt)-based chemo-regimens have been proved effective in neoadjuvant and salvage chemotherapy of triple negative breast cancer (TNBC).
0 kommentar(er)
