A phase II randomized trial of gemcitabine plus cisplatin (GP) versus gemcitabine plus carboplatin (GC) as the first-line treatment of patients with metastatic triple-negative breast cancer

Background: Platinum-based regimens play an essential role in triple-negative breast cancer (TNBC) treatment, with the CBCSG006 study establishing the position of gemcitabine plus cisplatin (GP) as a first-line treatment of metastatic TNBC.Our study aims to further improve the efficacy of the first-line platinum-based chemotherapy for metastatic TNBC by optimizing the selection of platinum.Patients and methods: A prospective, randomized, controlled phase II clinical trial was conducted to compare the efficacy and safety of the GP regimen with those of the gemcitabine plus carboplatin (GC) regimen as first-line treatment of patients with metastatic TNBC.A total of 150 untreated metastatic TNBC patients were enrolled and randomized 1 : 1 to receive either the GP or GC regimen until disease progression or intolerable toxicity.The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival, objective response rate (ORR), and safety.Results: After a median follow-up of 57.1 months (interquartile range 42.0-85.7 months), the median PFS for the GP and GC regimen was 7.8 months and 7.0 months, respectively (stratified hazard ratio 0.86; 95% confidence interval 0.59-1.25;P = 0.43); median overall survival was 20.3 months and 19.3 months, respectively (stratified hazard ratio of 1.05; 95% confidence interval 0.73-1.52;P = 0.79).The ORR of the GP regimen was higher than that of the GC regimen (49.3% versus 41.3%, P = 0.33).Grade 3-4 non-hematological adverse events (including nausea, vomiting, and hearing impairment) was more common in the GP group.The incidence of grade 3-4 hematological adverse events (including leukemia, thrombocytopenia, neutropenia, and anemia) was slightly higher in the GC group.No treatment-related death was reported in this study.Conclusions: Cisplatin was not associated with a survival advantage over carboplatin when combined with gemcitabine as a first-line treatment of patients with metastatic TNBC, though numerically longer PFS and higher ORR were observed.Differences in safety profiles may help guide individualized treatment decisions.