Neoadjuvant, anthracycline-free chemotherapy with carboplatin and docetaxel in triple-negative, early-stage breast cancer: a multicentric analysis of rates of pathologic complete response and survival

Introduction: Triple-negative breast cancer (TNBC) has the highest mortality rates of all subtypes. Anthracycline and taxane regimens yield unsatisfactorily low rates of pathologic complete response (pCR) and are often not feasible in cardiac comorbidity. This study seeks to increase pCR and survival by introducing platin agents. Patients and Methods: In this multicentric, open-label study with six cycles of docetaxel (75 mg/m2) and carboplatin AUC 6 q3w, patients were unwilling or unsuitable for anthracycline-based regimens. Primary endpoint was pCR (ypT0/ypTis ypN0) and survival. Results: pCR rate was 50%. After 2 and 5 years, overall survival (OS) was 96.7 and 89.7%, disease-free-survival (DFS) 96.7 and 85.7%, DDFS 96.7 and 89.6%. Grade 3/4 toxicities were rare. Ninety-three per cent of patients completed six cycles. No toxicity-related treatment discontinuation or febrile neutropaenia was recorded. Conclusion: This regimen is highly effective and feasible in TNBC and may be combined with anthracyclines.

[1]  I. Chirivella,et al.  Optimal delivery of anthracycline-based chemotherapy in the adjuvant setting improves outcome of breast cancer patients , 2009, Breast Cancer Research and Treatment.

[2]  F. Cognetti,et al.  HER2 and response to paclitaxel in node-positive breast cancer. , 2008, The New England journal of medicine.

[3]  G. Hortobagyi,et al.  Chemotherapy for Breast Cancer , 2008 .

[4]  K. Hess,et al.  Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  M. Piccart-Gebhart,et al.  Node positive breast cancer , 2003 .

[6]  M. Rezai,et al.  A randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). , 2013 .

[7]  C. Denkert,et al.  Effect of neoadjuvant anthracycline–taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study , 2010, Breast Cancer Research and Treatment.

[8]  Gideon Blumenthal,et al.  Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis , 2014, The Lancet.

[9]  E. Perez,et al.  Weekly paclitaxel in the adjuvant treatment of breast cancer. , 2008, The New England journal of medicine.

[10]  A. Schneeweiss,et al.  Abstract S3-1: Neoadjuvant Chemotherapy in the very young 35 years of age or younger , 2012 .

[11]  Tanja Fehm,et al.  Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. , 2012, The New England journal of medicine.

[12]  Larry Norton,et al.  HER2 and response to paclitaxel in node-positive breast cancer. , 2007, The New England journal of medicine.

[13]  Anthony Rhodes,et al.  American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. , 2010, Archives of pathology & laboratory medicine.

[14]  Debra L Winkeljohn Triple-negative breast cancer. , 2008, Clinical journal of oncology nursing.

[15]  A. Ashworth,et al.  Hallmarks of 'BRCAness' in sporadic cancers , 2004, Nature Reviews Cancer.

[16]  C. Perou,et al.  The Triple Negative Paradox: Primary Tumor Chemosensitivity of Breast Cancer Subtypes , 2007, Clinical Cancer Research.

[17]  Anthony Rhodes,et al.  American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. , 2006, Archives of pathology & laboratory medicine.

[18]  N. Rahman,et al.  Abstract S3-01: The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative orBRCA1/2breast cancer (CRUK/07/012) , 2015 .

[19]  J. Lubiński,et al.  Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  豊 木村,et al.  胃癌手術におけるCommon Terminology Criteria for Adverse Events v3.0を利用した合併症の評価 , 2009 .

[21]  R. Gelber,et al.  Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  James A Young,et al.  Bevacizumab added to neoadjuvant chemotherapy for breast cancer. , 2012, The New England journal of medicine.

[23]  E. Perez,et al.  Abstract S3-03: Ten year update of E1199: Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in patients with axillary node-positive or high-risk node-negative breast cancer , 2015 .

[24]  W. Sikov Assessing the Role of Platinum Agents in Aggressive Breast Cancers , 2015, Current Oncology Reports.

[25]  R. Carlson,et al.  Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies are clinicians responding optimally? , 2010, Journal of the American College of Cardiology.

[26]  Ian O Ellis,et al.  Prognostic markers in triple‐negative breast cancer , 2007, Cancer.

[27]  R. Gelber,et al.  Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[28]  P. Fasching,et al.  Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  S. Paik,et al.  Abstract PD2-1: The effect on overall and disease-free survival (OS & DFS) by adding bevacizumab and/or antimetabolites to standard neoadjuvant chemotherapy: NSABP Protocol B-40 , 2015 .

[30]  M. Rezai,et al.  Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. , 2014, The Lancet. Oncology.

[31]  S. Swain,et al.  Congestive heart failure in patients treated with doxorubicin , 2003, Cancer.

[32]  F. Heitz,et al.  Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases. , 2009, European journal of cancer.

[33]  R. Kimmig,et al.  Neoadjuvant, Anthracycline-Free Chemotherapy with Carboplatin and Docetaxel in Triple-Negative, Early-Stage Breast Cancer: A Multicentric Analysis of Feasibility and Rates of Pathologic Complete Response , 2014, Chemotherapy.

[34]  R. Cress,et al.  Descriptive analysis of estrogen receptor (ER)‐negative, progesterone receptor (PR)‐negative, and HER2‐negative invasive breast cancer, the so‐called triple‐negative phenotype , 2007, Cancer.

[35]  R. Witteles,et al.  Cancer therapy-induced left ventricular dysfunction: interventions and prognosis. , 2013, Journal of cardiac failure.

[36]  V. Kataja,et al.  Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  D. Berry,et al.  Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. , 2006, JAMA.

[38]  G. Hortobagyi,et al.  SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  S. Rodenhuis,et al.  Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers , 2013, British Journal of Cancer.

[40]  L. Carey,et al.  Triple-negative breast cancer: disease entity or title of convenience? , 2010, Nature Reviews Clinical Oncology.

[41]  D. Berry,et al.  Abstract S5-01: Impact of the addition of carboplatin (Cb) and/or bevacizumab (B) to neoadjuvant weekly paclitaxel (P) followed by dose-dense AC on pathologic complete response (pCR) rates in triple-negative breast cancer (TNBC): CALGB 40603 (Alliance) , 2013 .

[42]  Carsten Denkert,et al.  Response-guided neoadjuvant chemotherapy for breast cancer. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  L. Carey,et al.  What is triple-negative breast cancer? , 2008, European journal of cancer.

[44]  M. Rezai,et al.  Translating the concept of intrinsic subtypes into an oncoplastic cohort of more than 1000 patients - predictors of recurrence and survival. , 2015, Breast.

[45]  C. Geyer,et al.  Pathological Complete Response in Neoadjuvant Treatment of Breast Cancer , 2015, Annals of Surgical Oncology.

[46]  D. Berry,et al.  Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.