1. Single-agent nab-Paclitaxel Given Weekly (3/4) as First-line Therapy for Metastatic Breast Cancer (An International Oncology Network Study, #I-04-012) Barry Mirtsching 1, Thomas Cosgriff 2, Graydon Harker 3, Mark Keaton 4, Tarek Chidiac 5, Myo Min 6 1 Center for Oncology Research and Treatment, Dallas, TX; 2 Hematology Oncology Specialists, New Orleans, LA; 3 Utah Cancer Specialists, Salt Lake City, UT; 4 Augusta Oncology Associates, Augusta, GA; 5 Mid Ohio Oncology Hematology, Columbus, OH; 6 Maryland Hematology/Oncology Associates, Baltimore, MD Background: nab-Paclitaxel (Abraxane) for injectable suspension given weekly has shown activity in patients whose metastatic breast cancer was refractory to taxane therapy. The purpose of this Phase II study was to evaluate the efficacy and safety of administering nab- paclitaxel weekly to patients with locally advanced or metastatic breast cancer as first-line treatment. Methods: Patients  18 years with histologically or pathologically confirmed and documented locally advanced or metastatic breast cancer received nab-paclitaxel (125 mg/m 2 ) by 30-min IV infusion weekly for the first 3 weeks of each 4-week cycle. HER2- positive patients were allowed to receive trastuzumab (Herceptin). Results: At the time of analysis, 72 patients received study medication and 47 were evaluable for response. Patient characteristics include: gender male/female, 2/45; median age 59 years (range 36-84); ECOG performance status 0/1, 30/17; HER2 status +/- /missing, 17/29/1; and 27 patients (79.4%) had received prior chemotherapy. The median number of cycles administered was 5 (range 1-22) with a median weekly delivered dose of 125.0 mg/m 2 (range 78.1-163.4 mg). The treatment phase is complete and patients who remain on study are in follow-up. The primary endpoint is overall response rate (RR). The overall RR was 42.6% (95% CI, 28.3 to 57.8). Two HER2-positive patients had a CR and 9 patients had a PR (overall RR of 64.7%). Nine HER2-negative patients had a PR (overall RR of 31%). Median time to progression was 15.9 months (95% CI, 12.7 to 18.8) and median survival was 27.2 months (95% CI, 21.5 to not reached). Thirty-eight patients are alive. The most common toxicities (G3-4) were neutropenia (11.1%), infection (9.7%), neuropathy (8.3%), fatigue (4.2%), and nail disorder (4.2%). Conclusions: These results suggest that nab-paclitaxel is well tolerated as a first-line treatment of locally advanced or metastatic breast cancer. Moreover, a response rate of 42% is encouraging, particularly in the HER2-positive population where 64% of patients responded. Supported by Abraxis BioScience LLC Objectives Abstract Patient Selection Patient Characteristics Assessments Treatment Schedule Responses Patients received nab-paclitaxel 125mg/m 2 (given as a 30-minute infusion) on days 1, 8, and 15 for the first 3 weeks of each cycle. Trastuzumab was given concurrently with study treatment for patients who were HER2-positive. Cycles were repeated every 4 weeks. Estimated Overall Survival Toxicities Single-agent weekly nab-paclitaxel was associated with a response rate of 42.6% and an overall benefit of 93.6% as a first-line treatment of metastatic breast cancer. In addition, the median time to progression of 15.9 months, and 27% overall survival at 36 months demonstrates significant efficacy of weekly nab-paclitaxel in this population. Our results also suggest that nab-paclitaxel has a favorable safety profile in patients with metastatic breast cancer. Time to Progression The following assessments were performed at baseline, throughout study treatment, and at the completion of therapy: CT scans, MRIs, and x-rays (performed every 2 cycles) Physical examination and neurologic assessment ECOG performance status CBC, serum chemistry, and electrolytes performed at regular intervals Toxicity assessment HER2-positive patients receiving trastuzumab underwent cardiac monitoring and LVEF assessment via echocardiogram or MUGA scan at regular intervals. Eligibility Requirements: Histologically or pathologically documented locally advanced or metastatic breast cancer. Patients could be HER2-positive or HER2-negative. Measurable disease per RECIST criteria Disease that was not amenable to potentially curative resection Age ≥18 years ECOG performance status of 0 or 1 Adequate bone marrow, hepatic, and renal function No prior chemotherapy for metastatic disease (prior adjuvant chemotherapy was allowed provided it was completed > 12 months prior to enrollment) No prior treatment with nab-Paclitaxel Conclusions Prior Treatment The median number of cycles was 5 (range: 1-22). 1: Subjects may have more than one prior treatment. # 6073 Study Objectives: Response rate Time to progression One-year and two-year survival Overall safety profile This is a Phase II, open-label, non-randomized study. Patients were stratified by HER2 status (20 HER2-positive patients and 50 HER2-negative patients). Time (months) % Subjects without PD Time (months) % Survival Median Progression Free Survival 15.9 mos (95% CI, 12.7 to 18.8) Median Overall Survival 27.2 mos (95% CI, 21.5 to not reached) One-year survival = 79% Two-year survival = 59%