First-Line Gemcitabine/Docetaxel vs Doxorubicin in Advanced Soft-Tissue Sarcoma
In the UK-Swiss phase III GeDDiS trial, the combination of gemcitabine and docetaxel did not significantly improve progression-free survival vs doxorubicin in first-line treatment of locally advanced or metastatic soft-tissue sarcoma. Findings were reported in The Lancet Oncology by Seddon et al.
Study Details
In the trial, 257 patients with no prior exposure to doxorubicin from 24 UK sites and 1 Swiss site were randomized between December 2010 and January 2014 to receive gemcitabine at 675 mg/m2 on days 1 and 8 and docetaxel at 75 mg/m2 on day 8 every 3 weeks (n = 128) or 6 cycles of doxorubicin at 75 mg/m2 on day 1 every 3 weeks (n = 129). Randomization was stratified by age and histologic subtype. The primary endpoint was the proportion of patients alive and progression free at 24 weeks in the intention-to-treat population.
Progression-Free Survival
Median follow-up was 22 months. The proportion of patients alive and progression free at 24 weeks was 46.4% in the gemcitabine/docetaxel group vs 46.3% in the doxorubicin group (no significant difference); median progression-free survival was 23.7 weeks vs 23.3 weeks (unadjusted hazard ratio [HR] = 1.28, P = .06; HR after adjustment for histologic subtype = 1.26, P = .08). Exploratory subgroup analyses showed no difference in treatment effect according to histologic subtype (P = .24), leiomyosarcoma vs other sarcomas (P=.14), or uterine leiomyosarcoma vs other sarcomas (P = .38). Overall survival at 24 weeks was 82.6% vs 86.8%, and median overall survival was 67.3 weeks vs 76.3 weeks (unadjusted HR = 1.14, P = .41). Objective response rate was 20% vs 19%.
Adverse Events
The most common grade 3 or 4 adverse events were neutropenia (20% in the combination group vs 25% in the doxorubicin group), febrile neutropenia (12% vs 20%), fatigue (14% vs 6%), oral mucositis (2% vs 14%), and pain (10% vs 8%). The three most common serious adverse events were febrile neutropenia (12% of 130 serious events in the combination group vs 17% of 155 in the doxorubicin group), fever (15% vs 12% of events), and neutropenia (8% vs 14% of events).
The investigators concluded: “Doxorubicin should remain the standard first-line treatment for most patients with advanced soft-tissue sarcoma. These results provide evidence for clinicians to consider with their patients when selecting first-line treatment for locally advanced or metastatic soft-tissue sarcoma.”
The study was funded by Cancer Research UK, Sarcoma UK, and Clinical Trial Unit Kantonsspital St Gallen.
Beatrice Seddon, PhD, of the University College London Hospitals NHS Foundation Trust, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
