In vivo response-adapted dose-dense (dd) doxorubicin and cyclophosphamide (AC) -> weekly carboplatin and albumin- bound paclitaxel (nab-TC) plus trastuzumab (H) or bevacizumab (B) in patients with large and inflammatory breast cancer (BC): A phase II study

Abstract

11569 Background: In prior studies (ASCO 2005–07) at our institution, a 72% (21/29, 10/15 [67%] AC-resistant subset) pathologic complete response (pCR) with dd AC ->weekly (wkly) cemophor (c)-TCH in HER2+BC in contrast to 27% (9/35) pCR with dd AC->c-TC in HER2-BC was achieved. We substituted nab-T for c-T in all and added B in HER2-BC to exploit the preclinical synergy between nab-T and B in the current study (prelim. ASCO 2007). Methods: Patients (pts) with stage II-IV BC were enrolled with median age of 51 (range 28–76). Pts received in vivo response-adjusted AC (8 completed 4 and 35 ≤ 2 cycles) ->wkly 9–12 nab-T at 100 mg/m2 and C (AUC of 2), both 3 wks on, 1 wk off. HER2+ pts received concurrent 16 wkly H (4mg/kg induction, 2mg/kg maintenance) and HER2- pts received 6–8 bi-wkly B (10 mg/kg). Results: Adverse event with dd AC included neutropenic fever in 3 pts (2 on pegfilgrastin, 1 on GM-CSF). One (with CVD) of 15 pts treated with nab-TCH had asymptomatic grade III decline in ejection fraction. Median EF on baseline was 66% (59–78%), post 2 AC 68% (56–84%) and post nab-TCH 63% (47–68%). pCR was documented in 5/15 (33%) AC-resistant HER2+, 7 of 28 (25%) HER2-, 0/9 lobular/mixed ductal&lobular, 5/11(45%) HR-, 7/29 (24%) HR+, and 0/3 metaplastic BC. Ten additional tumors were reduced to ≤ 5 mm. Progression-free survival at a median follow-up of 18 months (range 10–27 months) is 81%, and 97% after excluding stage IV progressors (7 of 10 stage IV pts progressed). Only one pt with stage IIIB metaplastic BC has died. Conclusions: The lower pCR rate in the current study compared to the prior study in HER2+BC may be due to higher percentage of HR+ and lobular BC, and requirement of AC-sensitivity documentation by all modalities as compared to documentation by one modality in prior study. This limited AC administration to 2 cycles in all HER2+ pts. However, the lower rate of pCR in AC-resistant HER2+BC is still higher than historical AC-resistant BC (2–7%), showing that cTCH (pCR rate 67%) or nab-TCH (pCR rate 32%) are effective in AC-resistant HER2+BC. The addition of bevacizumab did not achieve a higher pCR rate compared to prior study in HER2-BC with cTC. No significant financial relationships to disclose.