Neoadjuvant docetaxel plus cisplatin versus docetaxel plus doxorubicin and cyclophosphamide in early-stage triple-negative breast cancer (HELEN-001): results from a multicenter, randomized controlled, open-label phase II trial

Abstract Background Adding platinum to anthracycline- and taxane-based neoadjuvant chemotherapy has improved pathological complete response (pCR) and event-free survival(EFS) in patients with triple-negative breast cancer (TNBC). However, the efficacy for TNBC of combining taxane and platinum without anthracycline remains controversial. Methods The HELEN-001 trial was a randomized, phase 2 controlled, and open-label investigation carried out in China at 6 hospitals. Participants who were aged 18–70 years old, were histologically confirmed for TNBC clinical stage II–III, suitable for potentially curative surgery, and had an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 were selected for this trial. Participants were randomized into two equal groups; those who received docetaxel plus cisplatin (75 mg/m2, respectively) and those who received docetaxel plus doxorubicin and cyclophosphamide (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2). These regimens were given every 3 weeks for 6 cycles. Randomization was stratified by tumor size and nodal status. The primary endpoint was the number of individuals achieving a pCR (ypT0/isN0). The trial was registered with chictr.org (number ChiCTR-1800019501). Findings: Between November, 2018, and June, 2022, 212 patients were selected (n = 106/treatment arm). The number of individuals who achieved pCR after docetaxel plus cisplatin treatment was 51.9%, and that of those who attained pCR after docetaxel plus doxorubicin and cyclophosphamide was 35.8% (P = 0.019). After median follow-up of 29 monthsinterquartile range (IQR), 21 to 41, 14 of 106 patients (13.2%) in the docetaxel plus cisplatin group and 18 of 106 patients (17.0%) in the docetaxel plus doxorubicin and cyclophosphamide group had event-free survival (EFS) events 95% confidence interval (CI) = 0.377 to 1.526, hazard ratio (HR) = 0.759, P = 0.492. The incidence of grade 3 or 4 events was similar in both groups 57 (54%) vs. 51 (48%). No treatment-associated deaths were identified in both groups. Interpretation: In stage II to III TNBC, the docetaxel plus cisplatin regimen achieved higher pCR rates than docetaxel plus doxorubicin and cyclophosphamide, with a comparable toxicity profile. Consistent with literature, the taxane plus cisplatin regimen demonstrated a favorable risk-to-benefit profile and could serve as an optimal neoadjuvant chemotherapy option for patients with high-risk TNBC.