Pathologic complete response (pCR) with weekly nanoparticle albumin bound (nab-P) plus carboplatin (C) followed by doxorubicin plus cyclophosphamide (AC) with concurrent bevacizumab (B) for triple-negative breast cancer (TNBC).

Abstract

1068 Background: TNBC are mostly “basal-like” tumors, that have been shown to overexpress Secreted Protein Acidic and Rich in Cysteine (SPARC). Endothelial transcytosis of nab-P via albumin- gp60 -cav1 and binding of albumin to SPARC results in high intratumoral levels of nab-P. Exploiting this and the dysfunctional DNA repair in basal tumors, we hypothesized that nab-P + C would produce high rates of pCR in TNBC, further enhanced by antiangiogenesis properties of B. Methods: Eligible women had operable TNBC ≥ 2 cm. pCR in the breast and pCR in the breast + nodes were primary & secondary end points respectively. We needed 57 evaluable patients to demonstrate 40% pCR vs. 25% (P0) in a single stage phase II design (α: 0.05, β: 0.2).Schema: C AUC 6 d1 + nab-P 100mg/m2d 1, 8 & 15 Q 28 d x 4 cycles followed by AC d1, Q14d x 4 cycles preoperatively with B 10mg/kg Q 14d for the first 6 cycles of preoperative chemotherapy, resuming postoperatively to complete 1 year of treatment.Baseline tumor biopsies & serial serum/blood samples were collected. Results: Due to slow accrual, study was closed after 42 patients. They were women between 35 and 68 years of age (median 52); 51% were African American and 46% were node positive. Safety population: N=41. Four patients came off study prior to surgery while 7 are still on pre-op treatment. Grade ¾ hematologic AEs: neutropenia (Gr3: 56%; Gr4:24%) febrile neutropenia (4%), thrombocytopenia (32%), anemia (22%). 7 patients had SAEs, with 1 grade 5 event. To date, thirty of 31 patients who had surgery (efficacy population) are considered evaluable per protocol. In-breast pCR rates are 55% (17/31) and 56% (17/30) and the rates of pCR breast + nodes are 52% (16/31) and 53% (16/30), for the efficacy and evaluable populations respectively. Conclusions: Majority of the patients in our study achieved a pCR, which is among the highest rates reported compared to anthracyclines+ taxanes without B in TNBC. Correlative analyses are planned. An ongoing randomized intergroup study is evaluating the individual contributions of carboplatin & bevacizumab to pCR in TNBC. Clinical trial information: NCT00777673.

The role of taxanes in triple-negative breast cancer: literature review

“…Grade 4 neutropenia was higher with nab-paclitaxel. This study is small, as stated by the authors, with just two TNBC cases, but it confirms the study by Snider et al 83 regarding the need of growth factors use when combining a taxane with carboplatin. The strength of this combination is the absence of anthracycline, which is interesting for cardiopathic patients.…”

“…Another interesting Phase II study of neoadjuvant treatment 83 involved 42 patients with TNBCs >2 cm treated with nab-paclitaxel at 100 mg/m 2 was given on days 1, 8, and 15, and carboplatin (AUC =6) day 1, every 4 weeks for four cycles, followed by doxorubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 , “dose-dense” every 14 days. Bevacizumab 10 mg/kg was administered every two weeks with chemotherapy, and continued postoperatively for a total of 1 year.…”