title: SOLTI NeoPARP: a phase II randomized study of two schedules of iniparib plus paclitaxel versus paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer.
abstract: Iniparib is an investigational agent with antitumor activity of controversial mechanism of action. Two previous trials in advanced triple-negative breast cancer (TNBC) in combination with gemcitabine and carboplatin showed some evidence of efficacy that was not confirmed. This phase II randomized neoadjuvant study was designed to explore its activity and tolerability with weekly paclitaxel (PTX) as neoadjuvant treatment in TNBC patients. 141 patients with Stage II-IIIA TNBC were randomly assigned to receive PTX (80 mg/m(2), d1; n = 47) alone or in combination with iniparib, either once-weekly (PWI) (11.2 mg/kg, d1; n = 46) or twice-weekly (PTI) (5.6 mg/kg, d1, 4; n = 48) for 12 weeks. Primary endpoint was pathologic complete response (pCR) in the breast. pCR rate was similar among the three arms (21, 22, and 19 % for PTX, PWI, and PTI, respectively). Secondary efficacy endpoints were comparable: pCR in breast and axilla (21, 17, and 19 %); best overall response in the breast (60, 61, and 63 %); and breast conservation rate (53, 54, and 50 %). Slightly more patients in the PTI arm presented grade 3/4 neutropenia (4, 0, and 10 %). Grade 1/2 (28, 22, and 29 %), but no grade 3/4 neuropathy, was observed. There were no differences in serious adverse events and treatment-emergent adverse events leading to treatment discontinuation among the three arms. Addition of iniparib to weekly PTX did not add relevant antitumor activity or toxicity. These results do not support further evaluation of the combination of iniparib at these doses plus paclitaxel in early TNBC.
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain. allombart1@yahoo.com.|Medical Oncology, Arnau de Vilanova Hospital, Valencia, Spain. allombart1@yahoo.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Cussac
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Medical Oncology, University Clinic Hospital, Valencia, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Bermejo
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Universitary Hospital of Besançon, Besançon, France.
authors.forename: Cristian
authors.initials: C
authors.lastname: Villanueva
authors.affiliation: Gustave Roussy Institute, Villejuif, France.
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Medical Oncology, Arnau de Vilanova Hospital, Lleida, Spain.
authors.forename: Serafín
authors.initials: S
authors.lastname: Morales
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Balmaña
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Medical Oncology, Sant Joan de Reus Hospital, Reus, Spain.
authors.forename: Kepa
authors.initials: K
authors.lastname: Amillano
authors.affiliation: Institut Bergonié, University of Bordeaux, INSERM U916, Bordeaux, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bonnefoi
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Medical Oncology, Virgen del Rocío Hospital, Sevilla, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Casas
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Medical Oncology, 12 de Octubre Hospital, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Manso
authors.affiliation: Institut Claudius Regaud, Toulouse, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Medical Oncology, Cáceres Hospital, Cáceres, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Gonzalez-Santiago
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Medical Oncology, Valencia Oncology Institute, Valencia, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Gavilá
authors.affiliation: Medical Oncology, Jaen Hospital, Jaen, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez-Rovira
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Di Cosimo
authors.affiliation: Department of OB&GYN, Breast Center, University of Munich, Munich, Germany.
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.affiliation: Sanofi Oncology Division, Cambridge, MA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Charpentier
authors.affiliation: Sanofi Oncology Division, Cambridge, MA, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garcia-Ribas
authors.affiliation: Pathology Department, Jean Perrin Center, Clermont-Ferrand, France.|EA 4677 ERTICA University of Auvergne, Clermont-Ferrand, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Radosevic-Robin
authors.affiliation: Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Aura
authors.affiliation: SOLTI Breast Cancer Research Group, Barcelona, Spain.|Breast Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D001549:Benzamides; C090712:iniparib; D017239:Paclitaxel
keywords: Breast cancer; Iniparib; Neoadjuvant chemotherapy; Paclitaxel; Triple-negative breast cancer