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Purpose:Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC.Patients and Methods:One-hundred and ninety patients with stage I–III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan–Meier method.Results:Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14–0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10–0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS.Conclusions:Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

Pathological response to carboplatin plus docetaxel by germline BRCA status

Purpose: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC.Experimental Design: The study population includes 190 patients with stage I–III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated.Results: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event.Conclusions: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline–taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649–57. ©2016 AACR.

Recurrence-free survival and overall survival in the overall patient population

Recurrence-free survival and overall survival by adjuvant chemotherapy use in RCB II/III patients

Further description of patient population and exploratory analysis.

Purpose:Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC.Patients and Methods:One-hundred and ninety patients with stage I–III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan–Meier method.Results:Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14–0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10–0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS.Conclusions:Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

Purpose: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. Experimental Design: The study population includes 190 patients with stage I–III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated. Results: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. Conclusions: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline–taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649–57. ©2016 AACR.