title: Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early-stage breast cancer (NCT01372579).
abstract: The purpose of this study is to evaluate the efficacy and safety of neoadjuvant treatment with carboplatin and eribulin in patients with early-stage triple negative breast cancer (TNBC), and to explore biomarkers based on DNA and protein expression profiles as predictors of response. Patients with histologically confirmed early-stage TNBC received carboplatin AUC 6 iv every 21 days, and eribulin 1.4 mg/m(2) day 1 and day 8 every 21 days for four cycles. The primary endpoint of the study was pathologic complete response (pCR), with secondary endpoints including clinical response and safety of the combination. Exploratory studies assessed DNA-based biomarkers [homologous recombination deficiency (HRD) score, and HR deficiency status (HRD score + BRCA1/BRCA2 mutation status)], protein-based biomarkers (Ki67, TP53, androgen receptor, Cyclin E, CDK2, Cyclin D, CDK4, Pin1 and Smad3), and clinical pretreatment factors as predictors of pCR. 13/30 (43.3 %) patients enrolled in the study achieved pCR. 24 (80.0 %) had a clinical complete or partial response. The combination was safe with mostly grade 1 and 2 toxicities. HRD score (P = 0.0024) and HR deficiency status (P = 0.0012) significantly predicted pCR. Pretreatment cytoplasmic CDK2 was also associated with pCR (P = 0.021). Significant differences in pre- versus post-treatment expression levels of nuclear Cyclin D (P = 0.020), nuclear CDK4 (P = 0.0030), and nuclear Smad3 (P = 0.015) were detected. The combination of carboplatin and eribulin is safe and efficacious in the treatment of early-stage TNBC. HRD score, HR deficiency status, and cytoplasmic CDK2 predicted pCR in this patient population.
authors.affiliation: Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA, vkaklamani@gmail.com.
authors.forename: Virginia G
authors.initials: VG
authors.lastname: Kaklamani
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Jeruss
authors.forename: Elisha
authors.initials: E
authors.lastname: Hughes
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Siziopikou
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Timms
authors.forename: Alexander
authors.initials: A
authors.lastname: Gutin
authors.forename: Victor
authors.initials: V
authors.lastname: Abkevich
authors.forename: Zaina
authors.initials: Z
authors.lastname: Sangale
authors.forename: Cara
authors.initials: C
authors.lastname: Solimeno
authors.forename: Krystal L
authors.initials: KL
authors.lastname: Brown
authors.forename: Joshua
authors.initials: J
authors.lastname: Jones
authors.forename: Anne-Renee
authors.initials: AR
authors.lastname: Hartman
authors.forename: Caitlin
authors.initials: C
authors.lastname: Meservey
authors.forename: Borko
authors.initials: B
authors.lastname: Jovanovic
authors.forename: Irene
authors.initials: I
authors.lastname: Helenowski
authors.forename: Seema A
authors.initials: SA
authors.lastname: Khan
authors.forename: Kevin
authors.initials: K
authors.lastname: Bethke
authors.forename: Nora
authors.initials: N
authors.lastname: Hansen
authors.forename: Regina
authors.initials: R
authors.lastname: Uthe
authors.forename: Sara
authors.initials: S
authors.lastname: Giordano
authors.forename: Steven
authors.initials: S
authors.lastname: Rosen
authors.forename: Kent
authors.initials: K
authors.lastname: Hoskins
authors.forename: Jamie
authors.initials: J
authors.lastname: Von Roenn
authors.forename: Sarika
authors.initials: S
authors.lastname: Jain
authors.forename: Vamsi
authors.initials: V
authors.lastname: Parini
authors.forename: William
authors.initials: W
authors.lastname: Gradishar
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D005663:Furans / Q000008:administration & dosage; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D053208:Kaplan-Meier Estimate; D007659:Ketones / Q000008:administration & dosage; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000095662:Polyether Polyketides
chemical_list: D015415:Biomarkers; D016190:Carboplatin; D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides