Multicenter phase 2 trial of pembrolizumab and paclitaxel in HR+/HER2- metastatic breast cancer with HER2-enriched or basal-like subtypes

HR-positive, HER2-negative metastatic breast cancer (HR+/HER2- mBC) is biologically distinct from early-stage disease, with a higher prevalence of genomically defined non-luminal subtypes, particularly the HER2-enriched (HER2-E) and basal-like subtypes. These tumors are associated with poor outcomes and early resistance to endocrine therapy and CDK4/6 inhibition CDK4/6i). The multicenter phase 2 SOLTI-1716 TATEN trial in Spain evaluated the combination of pembrolizumab and paclitaxel in patients with HR+/HER2- mBC classified as HER2-E or basal-like by PAM50 following progression on CDK4/61. Twenty patients received pembrolizumab (200 mg every 3 weeks) and paclitaxel (80 mg/m² weekly). The primary endpoint, overall response rate, was 61.1% (95% CI 35.7-82.7) and the clinical benefit rate was 94.4% (72.7-99.9); median progression-free survival was 8.1 months (5.9-10.4) and median overall survival was 26.0 months (18-NR). Three patients (15%) achieved durable responses lasting ≥ 24 months. The authors conclude that these results suggest that chemo-immunotherapy may be an effective strategy in genomically defined non-luminal subtypes of HR+/HER2- mBC following CDK4/6i resistance.