Abstract P3-14-07: Carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer - A phase II clinical trial

Abstract

Abstract Background Combination anthrathyclin-taxane regimens are the most widely-used neoadjuvant chemotherapy for triple negative breast cancer (TNBC), with objective response rates (ORR) of approximately 80% but poor pathologic complete response rates (pCR, 10%-25%) and survival. More effective chemotherapy regimens are needed. Several small clinical trials have suggested cisplatin- or carboplatin-containing chemotherapy can achieve higher pCR rates. However, no studies have compared the efficacy of platinum combination chemotherapy with a traditional anthrathyclin-taxane regimen. The objective of this study is to compare carboplatin plus paclitaxel with epirubicin plus paclitaxel in the neoadjuvant setting to determine the better choice for TNBC. Methods This is a single centre, open label, two-arm phase II clinical trial (NCT01276769). Patients with ER/PR/Her-2 negative breast cancer by immunohistochemistry from core needle biopsy were enrolled. All had indication for neoadjuvant chemotherapy. Patients were stratified according to clinical stage (II/III), and then randomized to receive paclitaxel (175 mg/m2, d1) and carboplatin (AUC = 5, d2), every 3 weeks for 4-6 cycles (PC arm) or epirubicin (75mg/m2, d1) plus paclitaxel (175 mg/m2, d2), every 3 weeks for 4-6 cycles (EP arm). The primary endpoint was pCR, which was defined as no residual invasive cancer in both the excised breast and axillary lymph node, or only carcinoma in situ. The secondary endpoints included ORR, safety, RFS (relapse-free survival) and OS (overall survival). Results A total of 91 patients were recruited (PC 47 patients, EP 44 patients) from April 2006 to December 2012. Median age was 47 years (range 24-73); 65% patients were premenopausal; 66% were at stage III; CK5/6 and EGFR positive rates were 63.01% (46/73), and 79.73% (59/74), respectively. 77.03% (57/74) had Ki-67 scores ≥ 20%. The proportion of patients with basal-like subtype (defined as CK5/6 or EGFR positive) in the two arms was 97.30% vs. 91.67 (p = 0.358). Eighty-five percent of patients completed 4-6 cycles of chemotherapy. ORR in the PC and EP arm was similar (89.4% vs. 79.6%, P = 0.195), but the pCR rate in the PC arm was significantly higher compared to the EP arm (38.6% vs. 14.0%, p = 0.016). The main G3/4 adverse event in both arms was neutropenia (72.3% vs. 63.6%, p = 0.500). Median follow-up period was 37 months (range 3-78 months), and 8 and 17 RFS events occurred in the PC and EP arms, respectively. Eighty-eight percent (22/25) of death events occurred in the first 3 years after diagnosis. Four-year RFS in the PC and EP arms were 71.1% vs. 52.8%, respectively (p = 0.080), and 4-year OS were similar (70.1% vs. 72.5% respectively, p = 0.980). For the whole group, pCR patients had significantly better 4-year RFS (90.9% vs. 50.1%, p = 0.001) and 4-year OS (100% vs. 64.9%, p = 0.002) compared with non-pCR patients. Conclusion Compared with the most widely-used EP chemotherapy, the PC regimen could significantly improve pCR rate for TNBC, and the 4- year RFS showed a trend towards improvement. Overall, pCR patients’ prognosis was much better than non-pCR patients. PC chemotherapy could be the preferred choice for TNBC neoadjuvant treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-07.