Randomized phase 2 trial of first-line subtype-based therapy for recurrent or metastatic triple-negative breast cancer

Triple-negative breast cancers (TNBCs) display heterogeneity in molecular drivers and immune traits. TNBCs can be classified into four subtypes: luminal androgen receptor (LAR) , immunomodulatory, basal-like immune-suppressed (BLIS), and mesenchymal-like (MES). The multicenter randomized phase 2 FUTURE-SUPER trial in China evaluated subtype-based first-line therapies for recurrent or metastatic (R/M) TNBCs. The study included 139 patients who were randomized to nab-paclitaxel only (control group; n=70) or nab-paclitaxel plus subtype-based agent (n=69): pyrotinib in LAR-HER2^mut, everolimus in LAR-PI3K/AKT^mut and MES-PI3K/AKT^mut, camrelizumab plus famitinib in the immunomodulatory subtype, and bevacizumab in BLIS/MES-PI3K/AKT^WT subtype. Primary endpoint was investigator-assessed progression-free survival in the pooled subtype-based group versus the control group. At median 22.5 months follow-up (IQR 15.2-29.0) the median PFS was 11.3 months in the subtype-based group verus 5.8 months in the control group (HR 0.44; p<0.0001). Treatment-related serious adverse events were reported for 10% of patients in the subtype-based group and none in the control group. No treatment-related deaths were reported. The authors conclude that these findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in TNBC.