Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Abstract

PURPOSE Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological 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. PATIENTS AND METHODS 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 Cb (AUC 6) + D (75mg/m2) given every 21 days × 6 cycles. Pathological complete response (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 35mm, 52% Lymph Node positive and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0+1 rates were 55% and 68%, respectively. pCR 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. 21% and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. CONCLUSION The CbD regimen was well tolerated and yielded high pCR rates in both BRCA associated and wildtype TNBC. These results are comparable to pCR achieved with addition of Cb 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.

Treatment strategies for DNA repair-deficient prostate cancer

“…The DNA damaged by the platinum agent is required to be repaired to restore the functionality of the cell, or cell death can result. Epithelial ovarian cancer and triple-negative breast cancer (both of which may be enriched for tumors with HRD) have clinical evidence of increased sensitivity to platinum chemotherapy compared to other chemotherapeutic agents and compared to tumors without mutations in homologous recombination repair pathway genes [38, 39, 40, 41]. Much of the development of PARP inhibition in ovarian cancer has focused on platinum-sensitive tumors, given the observations regarding underlying potential sensitivity to both treatments.…”

Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial

“…Hence, further predictive markers for chemotherapy (CHT) modification approaches are urgently needed. Moreover, carbo/taxane or gemcitabine (gem)/taxane, A‐free combinations also seem to be highly efficacious in early or metastatic TNBC . However, here as well, no predictive markers have yet emerged …”

Adjuvant Anthracyclines in Breast Cancer: What Is Their Role?

“…Longer‐term follow‐up and confirmatory data from subgroups at highest and lowest risk may help determine which patients stand to benefit from adjuvant anthracycline therapy. Future studies' randomized trials may evaluate other alternatives to an anthracycline regimen such as a platinum‐based nonanthracycline therapy for triple‐negative breast cancer, which has shown promising pCR rates as neoadjuvant therapy .

Despite the discordant study results, it is clear that the magnitude of benefit of adjuvant anthracyclines compared with a taxane regimen is small and may be primarily concentrated in patients with triple negative tumors or extensive lymph node involvement.

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