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


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 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.
University of Kansas Medical Center, Westwood, Kansas. psharma2@kumc.edu mmartin@geicam.org.
Priyanka
P
Sharma
Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Sara
S
López-Tarruella
Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
Jose Angel
JA
García-Saenz
University of Kansas Medical Center, Westwood, Kansas.
Claire
C
Ward
University of Kansas Medical Center, Westwood, Kansas.
Carol S
CS
Connor
Medical Oncology Department, Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú.
Henry L
HL
Gómez
Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain.|Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.|Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Aleix
A
Prat
Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
Fernando
F
Moreno
Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Yolanda
Y
Jerez-Gilarranz
Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Augusti
A
Barnadas
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Antoni C
AC
Picornell
Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Maria
M
Del Monte-Millán
Laboratory of Translational Oncology. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Milagros
M
Gonzalez-Rivera
Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Tatiana
T
Massarrah
Oncology Department, Hospital Clínico, Valladolid, Spain.
Beatriz
B
Pelaez-Lorenzo
Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
María Isabel
MI
Palomero
Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Ricardo
R
González Del Val
Department of Oncology, Ramon y Cajal University Hospital, Madrid, Spain.|Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Javier
J
Cortes
Medical Oncology Department, Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú.
Hugo
H
Fuentes Rivera
Medical Oncology Department, Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú.
Denisse
D
Bretel Morales
Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Iván
I
Márquez-Rodas
Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Charles M
CM
Perou
University of Kansas Medical Center, Westwood, Kansas.
Jamie L
JL
Wagner
University of Kansas Medical Center, Westwood, Kansas.
Joshua M V
JM
Mammen
University of Kansas Medical Center, Westwood, Kansas.
Marilee K
MK
McGinness
University of Kansas Medical Center, Westwood, Kansas.
Jennifer R
JR
Klemp
University of Kansas Medical Center, Westwood, Kansas.
Amanda L
AL
Amin
University of Kansas Medical Center, Westwood, Kansas.
Carol J
CJ
Fabian
University of Kansas Medical Center, Westwood, Kansas.
Jaimie
J
Heldstab
University of Kansas Medical Center, Westwood, Kansas.
Andrew K
AK
Godwin
University of Kansas Medical Center, Westwood, Kansas.
Roy A
RA
Jensen
University of Kansas Medical Center, Westwood, Kansas.
Bruce F
BF
Kimler
University of Kansas Medical Center, Westwood, Kansas.
Qamar J
QJ
Khan
Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. psharma2@kumc.edu mmartin@geicam.org.
Miguel
M
Martin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D000069585:Filgrastim / Q000627:therapeutic use; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007615:Kansas; D008408:Mastectomy; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D020360:Neoadjuvant Therapy; D064887:Observational Studies as Topic; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011446:Prospective Studies; D013030:Spain; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy
D043823:Taxoids; D000077143:Docetaxel; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D016190:Carboplatin; D000069585:Filgrastim