A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study

Abstract

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation–Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105

“…The GEICAM (Grupo Español de Investigación en Cáncer de Mama) 2006-03 study of epirubicin and cyclophosphamide followed by docetaxel with or without carboplatin showed no improvement in pCR with the addition of carboplatin. 25 In the phase II GeparSixto trial, which assessed a regimen of dose-intense anthracyclineand taxane-based chemotherapy with bevacizumab with or without carboplatin, patients receiving carboplatin achieved a pCR rate of 53.2% compared with 36.9% in patients who did not. 26 In the phase II CALGB 40603 (Cancer and Leukemia Group B) study of standard anthracycline/taxane-based chemotherapy with or without carboplatin and with or without bevacizumab, the addition of carboplatin significantly increased the pCR rate (breast and axilla) in the per-protocol population by 13% (pCR with carboplatin, 54% v without, 41%).…”

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)

“…, 18,19 GEICAM (Grupo Español de Investigació n del Cáncer de Mama) 2006-03, a much smaller trial (N ϭ 94), reported a nonsignificant drop in pCR (30% v 35%) when carboplatin was added to docetaxel after an anthracycline-based combination. 18 In GeparSixto (sixth German Preoperative trial), 315 patients with TNBC received wP 80 mg/m 2 , nonpegylated liposomal doxorubicin 20 mg/m 2 once per week, and bevacizumab 15 mg/kg every 3 weeks, with or without weekly carboplatin AUC 2,for 18 weeks.…”

“…18 In GeparSixto (sixth German Preoperative trial), 315 patients with TNBC received wP 80 mg/m 2 , nonpegylated liposomal doxorubicin 20 mg/m 2 once per week, and bevacizumab 15 mg/kg every 3 weeks, with or without weekly carboplatin AUC 2,for 18 weeks. 19 This regimen was associated with high rates of grade Ն 3 hematologic toxicities, especially in patients assigned to carboplatin, and early treatment discontinuation because of toxicity (control arm, 36%; carboplatin arm, 49%).…”

Platinum-based therapy for triple-negative breast cancer treatment: A meta-analysis

“…Four studies (18)(19)(20)(21) reported the pCR rate and five studies (18,(21)(22)(23)(24) reported the ORR in TNBC patients who were treated with a platinum-or a non-platinum-based regimen. There was significant heterogeneity between different study results (I 2 >50%, P<0.1), so the random-effects model was applied for data analysis.…”