Carboplatin (Cb), weekly nanoparticle, albumin-bound paclitaxel (wAb), and bevacizumab (Av) neoadjuvant chemotherapy (NAC) in HER2-negative breast cancer (BrCA): A BrUOG study.

Abstract

e11573 Background: To evaluate CbwAbAv NAC in HER2- BrCA. Methods: 60 patients (pts) with HER2- (IHC 0-1+ or FISH <2.0) invasive BrCA, clinical stage IIA-IIIC, will undergo research biopsies/MRI pre and post “priming” doses of Av or wAb, then receive q3wk Cb AUC 6, wAb 100 mg/m2 + Av 5 mg/kg/week x 12 weeks + (cohort 1)/- (cohort 2) dose-dense doxorubicin and cyclophosphamide (ddAC)Av x 4. Post-op, pts receive Av x 34 weeks; radiation, endocrine Rx, and ddACAv x 4 (cohort 2) at MD discretion. Endpoints include pathologic complete response (pCR - absence of invasive disease in breast + axillary nodes), residual cancer burden (RCB) in non-pCRs, dose delivery and toxicities. Circulating tumor/endothelial cells (CTC/CEC) at baseline and after priming are analyzed using the Veridex platform. Results: 39 pts (median age 47; range 25-69), 21 hormone receptor positive (HR+), 18 triple-negative (TN) have received a median of 11 wAb and 4 Cb doses, with dose reductions in 25% (wAb - neutropenia [ANC]) and 14% (Cb - thrombocytopenia (tcp)). Grade 3/4 toxicities include ANC (43%/39%), tcp (18%/7%), transaminitis, nausea and hypokalemia, with no grade >2 neuropathy. Serious adverse events (SAEs): febrile neutropenia (2), altered mental status, anemia, post-mastectomy tissue necrosis, GI bleed and grade 2 proteinuria. Pathologic responses are tabulated below (Table). At baseline, few pts (19%) had identifiable CTC, which did not correlate with response. Pts with higher CEC levels at baseline (median, 22 vs. 11, p=.087) or after priming (median, 31 vs. 14.5, p=.035) were more likely to achieve RCB 0-1. Conclusions: Neoadjuvant CbwAbAv is generally well tolerated and yields encouraging pathologic responses, especially in TN pts. Differences between cohorts suggest that longer duration NAC or the use of non-cross resistant regimens may improve pCR rate. Higher CEC levels at baseline or after initial therapy may be associated with improved pathologic response. Updated results will be presented. n pCR IA/IB II-III RCB 0-1 RCB 2-3 Total 39 13 (33%) 9 17 21 (54%) 18 Cohort 1 21 (12 TN) 12 (57%) 3 6 15 (71%) 6 Cohort 2 18 (6 TN) 1 (6%) 6 11 6 (33%) 12 HR+ 21 3 (14%) 2 16 6 (29%) 15 TN 18 10 (56%) 7 1 15 (83%) 3