Introduction: TNBC has the highest mortality of all BC subtypes. Neoadjuvant platinum added to the taxanes-antracycline chemotherapy has been reported to improve pathologic complete response (pCR) rate and survival in TNBC. Aim: To evaluate the efficacy and toxicity of the addition of weekly Cp to Pl and dose dense EC on the pCR rate in an open-label phase II study in stage II/III TNBC pts.
Patients and methods: Sixty three pts received dose dense P (80mg/m2/wk) concurrent with Cp (AUC=2) for 12 wks, added to two-weekly E (90mg/m2) and C (600mg/m2) for 4 cycles, and followed by surgery and radiotherapy. The primary endpoint was pCR in the breast and axilla. Additionally adverse events are registered. A correlative assessment of germ line mutations in HRD genes is ongoing. Pts are monitored for clinical response by magnetic resonance and mammography and also for relapse free survival and time to treatment failure. The study sample size has been calculated according to the optimal Simon’s two-stage design method. The target sample size was 63 patients with 80% power to detect a pCR rate of > or = 47% (α = 0.05).
Accrual to the study is completed and 63 eligible pts with operable, non-inflammatory stage II/III TNBC were included. Most pts were between 40 and 60 yr old and 49 out of 63 were stage T2. Forty percent were clinically node + and 68% were G3. Seventy three percent received breast conserving surgery. Thirty eight out of 63 pts (60%) achieved a pCR rate in the breast and axilla. In 52 evaluable pts for toxicity, the main toxicity for part 1 (Cp+P) of the combination was neutropenia G3/4 in 37 pts (71%) and for part 2 (EC) febrile neutropenia G3/4 in 18 pts (34%) despite primary prophylaxis, followed by thrombocytopenia G3/4 in 11 pts (21%). Only three pts had a neuropathy G3.
The addition of weekly carboplatinum to neoadjuvant dose dense paclitaxel and EC is feasible and a pCR rate in the breast and axilla as high as 60% in early TNBC pts is obtained. Correlation with genomic HRD deficiency is ongoing.
Clinical trial identification
Legal entity responsible for the study
Breast Cancer Task force on behalf of the BSMO (Belgian Society of Medical Oncology)
Amgen and Teva
All authors have declared no conflicts of interest.