Randomized phase II trial of three gemcitabine (GEM)-taxane combinations in metastatic breast cancer (MBC

Abstract

710 Background: Two-drug combinations of GEM and paclitaxel (P) or docetaxel (D) have shown promising efficacy in MBC. This study evaluated efficacy and safety of GEM plus single or split dose taxanes. Methods: Major eligibility criteria: tissue diagnosis of breast carcinoma; stage IV; prior anthracycline therapy; KPS ≥70; age ≥18; adequate bone marrow, liver and kidney function; written informed consent. Patients (pts) were randomized to receive: GEM 1250 mg/m2 D1+8 and P 175 mg/m2 as 3-hr infusion D1 (GP1); GEM 1000 mg/m2 D1+8 and P 100 mg/m2 as 1-hr infusion D1+8 (GP2); GEM 1000 mg/m2 D1+8 and D 40 mg/m2 as 1-hr infusion D1+8 (GD) in a 3-week cycle (8 cycles max). Primary endpoint was response rate; secondary endpoints were time to progression (TTP), time to treatment failure (TTTF), response duration and toxicity. Results: 210 pts were enrolled, 208 qualified for safety and time-to-event efficacy analysis, 204 for response assessment. Baseline variables were balanced across arms. Dominant site of disease was visceral in 70%; >50% had ≥3 organ sites of disease; all but 1 pt had previously received anthracyclines, 46% for MBC. Efficacy outcomes were similar in the 3 arms. Neutropenia was the main toxicity in each arm. Grade 4 neutropenia, Grade 3+4 anemia, febrile neutropenia, infection and diarrhea were higher for GD as were use of G-CSF, IV antibiotics and blood transfusions. There were 6 drug-related deaths (2.9%; 2 pts on GP1, 3 on GP2, 1 on GD), mostly from myelotoxicity complications. Conclusions: The three GEM-taxane regimens appear to have high efficacy and manageable toxicity in MBC after prior anthracycline therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Asian Operations Eli Lilly & Co. Eli Lilly & Co. Eli Lilly Singapore Pty Ltd. Eli Lilly and Company