Yun Wu

The optimal treatment regimen for breast cancer patients with gBRCA mutations remains controversial given the availability of numerous options, such as platinum-based agents, polymerase inhibitors (PARPis), and other agents. We included phase II or III RCTs and estimated the HR with 95% CI for OS, PFS, and DFS, in addition to the OR with 95% CI for ORR and pCR. We determined the treatment arm rankings by P-scores. Furthermore, we carried out a subgroup analysis in TNBC and HR-positive patients. We conducted this network meta-analysis using R 4.2.0 and a random-effects model. A total of 22 RCTs were eligible, involving 4253 patients. In the pairwise comparisons, PARPi + Platinum + Chemo was better than PARPi + Chemo for OS (in whole study group and in both subgroups) as well as PFS. The ranking tests demonstrated that PARPi + Platinum + Chemo ranked first in PFS, DFS, and ORR. Platinum + Chemo showed higher OS than PARPi + Chemo. The ranking tests for PFS, DFS, and pCR indicated that, except for the best treatment (PARPi + Platinum + Chemo) containing PARPi, the second and third treatments were platinum monotherapy or platinum-based chemotherapy. In conclusion, PARPi + Platinum + Chemo might be the best regime for gBRCA-mutated BC. Platinum drugs showed more favorable efficacy than PARPi in both combination and monotherapy.

HER2-positive breast cancer brain metastasis (BCBM) is an important clinical problem. A systematic review and network meta-analysis were conducted to compare the efficacy of tyrosine kinase inhibitors (TKIs) and antibody–drug conjugates (ADCs), two categories of emerging agents in this field. We implemented a comprehensive literature search of PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and abstracts of oncology conferences. A network meta-analysis following Bayesian approaches was performed. Pooled hazard ratios (HRs) and odds ratios (ORs) with credible intervals (CrIs) were calculated to estimate progression-free survival (PFS), overall survival (OS), and the incidence of central nervous system (CNS) disease progression. Sixteen studies were included. Pairwise comparisons of PFS showed salient divergency between T-DXd and the physician’s choice of treatment (HR 0.17; 95% CrI 0.03–0.82) or afatinib (HR 0.14; 95% CrI 0.02–1.00). T-DXd and T-DM1 ranked first regarding PFS and OS, respectively, followed by TKI-containing regimens. The incidence of CNS disease progression was analyzed separately according to baseline BCBM status, among which neratinib-containing regimens were most likely to rank the best. In conclusion, ADCs including T-DXd and T-DM1 showed better efficacy than TKIs in the survival outcomes for HER2-positive BCBM patients. Treatments based on neratinib or T-DM1 revealed favorable results in reducing the recurrent rate of CNS.