Phase II study of weekly nanoparticle albumin bound (nab)paclitaxel with carboplatin and trastuzumab as 1st-line therapy for HER2-positive metastatic breast cancer (MBC)

Abstract

1047 Background: The addition of carboplatin (Cb) to paclitaxel (P) and trastuzumab (T) improves response rate and time to progression (TTP) in HER2+ MBC (Robert N, JCO 2006). Weekly P+Cb+T is active and well-tolerated in patients (pts) with HER2+ MBC (Perez E, Clin Breast Cancer 2005). Nab-P is more active than Cremophor-based P (Gradishar W, JCO 2005). This study investigates the efficacy and safety of weekly nab-P+Cb+T. Methods: An initial cohort of 3 pts received nab-P at 75 mg/m2 i.v. followed by Cb at a target AUC=2 weekly (days 1, 8, 15 every 28 days) + T (4 mg/kg x 1, then 2 mg/kg on all weeks) for 1 cycle. This was well tolerated, thus nab- P was escalated to 100 mg/m2 for all subsequent cycles and pts. Neither prophylactic steroid nor antihistamine was given. Due to hypersensitivity reactions (HSRs) clearly attributable to Cb in 4 of the first 13 pts, Cb dosing was changed to once every 4 weeks (AUC=6) for the next 17 pts. P+Cb+T was continued until disease progression, unacceptable toxicity, or for 6 cycles with the option of continuing T alone at investigator discretion. Results: 30 pts were treated and 12 remain on study. The median age was 52 years (range, 29–76); 23 pts (77%) were post-menopausal and 20 pts (67%) had visceral-dominant MBC. 50% of pts had prior adjuvant chemotherapy, 30% with taxane. Mean number of cycles administered was 6.7 (range 1–16). The relative delivered dose intensity for nab-P was 80%. Grade 3 neutropenia occurred in 50% of pts, and was the only grade 4 toxicity (7%). Febrile neutropenia occurred in 1 pt (3%). Grade 3 non-hematologic toxicity was uncommon: fatigue (7%), nausea/emesis (7%). Neuropathy was mild and infrequent: grade 3 (3%) and grade 2 (7%). HSR was noted in only 1/17 pts receiving Cb monthly. 26 of 30 pts are evaluable for response. 12/26 pts (46%; 95% CI 27–65%) had a confirmed complete or partial response (2 CR, 10 PR). The median TTP is 16 months (95% CI 7–28). Efficacy was not dependent upon Cb schedule. Conclusions: Both the activity and the favorable toxicity profile support continued exploration of this regimen in a larger population for 1st-line treatment of HER2+ MBC. Weekly Cb in the absence of corticosteroid prophylaxis may be associated with a higher risk of HSR than monthly dosing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Abraxis, Abraxis Oncology, Bristol-Myers Squibb, Genentech™ BioOncology Abraxis, Abraxis Oncology, Genentech™ BioOncology