Phase II trial of neoadjuvant chemotherapy (NCT) with weekly nanoparticle albumin-bound paclitaxel (Nab-P), carboplatin (CBP), and bevacizumab (BEV) in women with clinical stages II-III breast cancer (BC): Pathologic response prediction by changes in angiogenic volume (AV) by dynamic contrast magnetic resonance imaging (DCE-MRI).

Abstract

604 Background: BEV in combination with paclitaxel improves the outcome of previously untreated metastatic BC patients (Miller et al NEJM 357, 2007). We hypothesized that adding BEV to weekly Nab-P and CBP as NCT would be well tolerated, have improved anti-tumor activity and early changes in AV by DCE-MRI would correlate with pathologic response. Methods: Pts with clinical stages II/III and HER2-non- overexpressing BC received Nab-P 100 mg/m2 IV and CBP AUC=2 IV on days 1, 8, and 15 in combination with BEV 10 mg/kg on days 1 and 15 administered every 28 days for 5 cycles; in the sixth cycle BEV was omitted. DCE-MRI was performed pre NCT, after 2 cycles and prior to the definitive surgery. Pathologic complete response (pCR) was defined as absence of invasive tumor in breast and axilla. Results: Thirty of planned 33 pts were enrolled. The median age was 48 years; 21 (70%) pts were premenopausal; 19 (63%) pts had ER/PR positive BC and 11 (37%) had triple negative BC (TNBC). Treatment was well tolerated with exception of grade 3 and 4 neutropenia in 14 (48%) and 2 (7%) and thrombocytopenia in 2 (7%) and 1 (3%) respectively. Thus far, 17 pts finished NCT; 12 (71%) received all 6 cycles with remaining 5 (29%) pts received < 3 cycles of NCT. The primary reason for not completing all 6 cycles was myelosuppression (n = 4) and disease progression (n = 1). Fourteen pts had definitive surgery: 6 (43%) had lumpectomy, and 8 (57%) had mastectomy. Three (21%) pts had pCR and 3 (21%) had microscopic residual disease (MRD). In the TNBC group the pCR rate was 50% (3 out of 6 pts). At the end of cycle 2, the relative AV decreased from 73% ± 10% in baseline DCE-MRI to 38% ± 37% in pts with pCR and MRD. The relative AV increased from 68% ± 25% in baseline DCE-MRI to 87% ± 18% in non-responders. The changes in relative AV were significantly different between responders and non-responders (p = 0.016). Conclusions: The combination was more myelosuppressive than expected. Early change in relative AV by DCE-MRI may predict response to NCT. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience, Roche