IS2-5 - Phase II Trial of TS-1 in Combination with Oxaliplatin (SOX) in Patients with Metastatic Breast Cancer (MBC) Previously Treated with Anthracycline and Taxane Chemotherapy [TORCH] [Korean Cancer Study Group (KCSG) BR07-03

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ABSTRACT Background Oxaliplatin, a platinum analogue, is an active drug in advanced anthracycline and taxane-pretreated breast cancer patients as a single agent and with 5-fluorouracil (5-FU) combination. TS-1 was developed by the scientific theory of both potentiating antitumor activity of 5-FU and reducing gastrointestinal toxicity. This trial was carried out to evaluate the efficacy and safety of TS-1 in combination with oxaliplatin in metastatic breast cancer (MBC) patients previously treated with anthracycline (A) and taxane (T) chemotherapy (CTx). Methods Between October 2007 and October 2009, MBC patients were enrolled in this prospective multicenter trial. Eligible criteria included age >18 years, at least one measurable lesion, prior treatment with A and T CTx, and ECOG PS 0-2. TS-1 40 mg/m2 bid on D1-14 with oxaliplatin 130 mg/m2 on D1 were administered every 3 weeks till disease progression. Primary end-point was response rate (RR), and secondary end-points were time-to-progression (TTP), overall survival (OS), duration of response (DOR) and toxic effects. Response was evaluated every 6 weeks according to the RECIST criteria v.1.0 and toxicity was assessed with NCICTCAE v.3.0. (ClinicalTrials.gov identifier NCT00527930.) Results A total of 87 patients were enrolled. Median age was 48 (range 30–71) years. Nineteen patients (21.8%) had de novo stage IV and 68 patients (78.2%) had recurrent disease. Forty-eight patients (55.2%) had ≥3 disease sites. Fifty-four patients (62.1%) were hormone receptor positive, and 25 patients (28.7%) were triple negative. Five patients received prior anti-HER2 therapy. A total of 525 cycles were administered (median 6, range: 1–22+ cycle). In per-protocol analysis, the overall RR was 38.5% (CR 0%, PR 38.5%) and the disease control rate (CR, PR, and SD) was 67.9%. Median TTP, OS, and DOR were 6.0, 19.4, 6.6 months, respectively. The RR did not differ by triple negativity (39.1% in TNBC versus 38.2% in non-TNBC, P = 0.361). Reported grade 3 or 4 toxic effects (per cycle) were neutropenia (10.3%), thrombocytopenia (5.5%), diarrhea (1.9%), vomiting (1.9%), and stomatitis (0.2%). There was no treatment-related death. Conclusions SOX is an effective regimen in anthracycline and taxane pretreated MBC patients with manageable toxic effects.