Japanese Study Shows Oral Fluoropyrimidine S-1 Is Noninferior to Taxanes as First-Line Treatment of HER2-Negative Metastatic Breast Cancer
In a Japanese phase III trial (SELECT BC) reported in The Lancet Oncology, Takashima et al found that first-line treatment with the oral fluoropyrimidine S-1 was associated with noninferior overall survival vs taxane regimens in women with HER2-negative metastatic breast cancer resistant to endocrine treatment.
Study Details
In the open-label trial, 618 patients from 154 hospitals in Japan were randomly assigned between October 2006 and July 2010 to receive docetaxel at 60 to 75 mg/m² every 3 to 4 weeks, paclitaxel at 80 to 100 mg/m² weekly for 3 of 4 weeks, or paclitaxel at 175 mg/m² every 3 to 4 weeks (n = 309) or S-1 at 40 to 60 mg twice daily for 28 consecutive days followed by 14 days off in each course (n = 309).
The primary endpoint was overall survival (prespecified noninferiority margin of 1.333 for the hazard ratio [HR]) in the full analysis set, consisting of all patients who received at least one study treatment and had all data after randomization. The full analysis set consisted of 286 patients in the taxane group and 306 patients in the S-1 group.
Overall Survival
Median follow-up was 34.6 months. Median overall survival was 35.0 months (95% confidence interval [CI] = 31.1–39.0 months) in the S-1 group vs 37.2 months (95% CI = 33.0–40.1 months) in the taxane group (HR = 1.05, 95% CI = 0.86–1.27, P = .015 for noninferiority). Median progression-free survival was 9.6 vs 11.0 months (HR = 1.18, 95% CI = 0.99–1.40). Overall, 87% and 84% of patients received subsequent second-line treatments, including a taxane in 43% of the S-1 group and oral fluorouracil in 57% of the taxane group.
Toxicity and Quality of Life
The most common grade ≥ 3 adverse events were neutropenia (7% of S-1 group vs3% of taxane group), fatigue (3% vs 4%), and edema (< 1% vs 4%). Adverse events led to dose reduction in 12% vs 11% of patients and to treatment discontinuation in 7% vs 7%. Treatment-related death occurred in two patients in the taxane group.
Quality of life assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core-30 showed better outcomes in the S-1 group in global health status (P = .039 for mean difference over 12 months), with significant benefits in each of five functional domains and two of nine symptom domains.
The investigators concluded: “S-1 is non-inferior to taxane with respect to overall survival as a first-line treatment for metastatic breast cancer. S-1 should be considered a new option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer.”
The study was funded by a Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan, and Taiho.
Hirofumi Mukai, MD, of the National Cancer Center Hospital East, Chiba, Japan, is the corresponding author for The Lancet Oncology article.
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