Randomized phase II trial of anthracycline-free and anthracycline-containing neoadjuvant carboplatin chemotherapy regimens in stage I-III triple-negative breast cancer (NeoSTOP).

Purpose: Addition of carboplatin (Cb) to anthracycline chemotherapy improves pathologic complete response(pCR), and carboplatin plus taxane regimens also yield encouraging pCR rates in TNBC. Aim of NeoSTOP multisite randomized phase II trial was to assess efficacy of anthracycline-free and anthracycline-containing neoadjuvant carboplatin regimens. Experimental Design: Patients aged ≥18 years with stage I-III TNBC were randomized(1:1) to receive either paclitaxel(P) weekly X12 plus Cb AUC6 Q21 days X4 followed by doxorubicin/cyclophosphamide(AC) Q14 days X4 (CbP->AC, Arm-A), or to Cb AUC6 + docetaxel(D) Q21 days X6 (CbD, Arm-B). Stromal tumor-infiltrating lymphocytes (sTILs) were assessed. Primary endpoint was pCR in breast and axilla. Other endpoints included RCB, toxicity, cost, and event-free and overall survival. Results: 100 patients were randomized; Arm-A (N=48) or Arm-B (N=52). pCR was 54% (95% CI:40%-69%) in Arm-A and 54% (95% CI:40%-68%) in Arm-B. RCB 0+I rate was 67% in both arms. Median sTILs density was numerically higher in those with pCR compared with residual disease (20% vs 5%, P=0.25). At median follow-up of 38 months, event-free and overall survival were similar in two arms. Grade 3/4 adverse events were more common in Arm-A compared to Arm-B, with the most notable differences in neutropenia (60% vs 8%, P AC, but with a more favorable toxicity profile and lower treatment-associated cost.