title: Multicentric neoadjuvant pilot Phase II study of cetuximab combined with docetaxel in operable triple negative breast cancer.
abstract: Systemic therapy for triple negative breast cancer (TNBC) is mostly based upon chemotherapy. Epithelial Growth Factor Receptor (EGFR) is overexpressed in around 50% of TNBC and may play a role in its pathogenesis. Consequently, we performed a multicentric pilot Phase II neoadjuvant trial of cetuximab (anti-EGFR antibody) combined with docetaxel for patients with operable, Stage II-III TNBC. Therapy consisted of weekly cetuximab (first infusion: 400 mg/m(2), then 250 mg/m(2)) combined with six cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Subsequently, all patients underwent surgery. The primary endpoint was pathological complete response (pCR) while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected in order to identify predictive biomarkers of efficacy and resistance. From a total of 35 accrued patients, 25 were assessable for pathologic response. The pCR rate was 24% [95% CI: 7.3-40.7]. Complete clinical response rate (cCR) was observed in 22% of cases. Conservative surgery was performed in 75% of patients. Toxicity, mostly cutaneous and hematologic, was manageable. The pre-therapy ratio between CD8+ and FOXP3+ tumor-infiltrating lymphocytes equal or higher than 2.75 was predictive of pCR: 43% versus 0%, p = 0.047. Cetuximab in combination with docetaxel displays a modest activity, but acceptable toxicity as neoadjuvant therapy of operable TNBC. Similarly to previous observations using panitumumab, another anti-EGFR antibody, the immune component of the tumor microenvironment may play an important role in predicting TNBC response to the neoadjuvant therapy.
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|Clinical and Translational Research Division, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|CIC 501, UMR 766, Clermont-Ferrand, France.|Medical Oncology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Nabholtz
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|Clinical and Translational Research Division, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|CIC 501, UMR 766, Clermont-Ferrand, France.
authors.forename: N
authors.initials: N
authors.lastname: Chalabi
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|Department of Biopathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: N
authors.initials: N
authors.lastname: Radosevic-Robin
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|Department of Biopathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: M M
authors.initials: MM
authors.lastname: Dauplat
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|Medical Oncology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Mouret-Reynier
authors.affiliation: Medical Oncology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: I
authors.initials: I
authors.lastname: Van Praagh
authors.affiliation: Oscar Lambret Comprehensive Cancer Centre, Lille, France.
authors.forename: V
authors.initials: V
authors.lastname: Servent
authors.affiliation: Lucien Neuwirth Institute, Saint-Etienne, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Jacquin
authors.affiliation: Medical Oncology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: K E
authors.initials: KE
authors.lastname: Benmammar
authors.affiliation: Medical Oncology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: S
authors.initials: S
authors.lastname: Kullab
authors.affiliation: Medical Oncology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|Oncauvergne Regional Oncology Network, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: M R K
authors.initials: MR
authors.lastname: Bahadoor
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|Clinical and Translational Research Division, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|LMB GenAuvergne Oncogenetics Department, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: F
authors.initials: F
authors.lastname: Kwiatkowski
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|Department of Biopathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: A
authors.initials: A
authors.lastname: Cayre
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|Clinical and Translational Research Division, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|CIC 501, UMR 766, Clermont-Ferrand, France.
authors.forename: C
authors.initials: C
authors.lastname: Abrial
authors.affiliation: Clinical and Translational Research Division, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|CIC 501, UMR 766, Clermont-Ferrand, France.|Medical Oncology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|EA 3846, University of Auvergne, Clermont-Ferrand, France.
authors.forename: X
authors.initials: X
authors.lastname: Durando
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|LMB GenAuvergne Oncogenetics Department, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Bignon
authors.affiliation: Clinical and Translational Research Division, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|Inserm UMR 990, Clermont-Ferrand, France.|University of Auvergne Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: P
authors.initials: P
authors.lastname: Chollet
authors.affiliation: ERTICA EA 4677, University of Auvergne, Clermont-Ferrand, France.|Department of Biopathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.
authors.forename: F
authors.initials: F
authors.lastname: Penault-Llorca
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000601:surgery; D000068818:Cetuximab / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D010865:Pilot Projects; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D000068818:Cetuximab
keywords: anti-EGFR therapy; neoadjuvant chemotherapy; pathological complete response; predictive biomarkers; triple negative breast cancer