GeDDiS Trial: Gemcitabine/Docetaxel Shows No Advantage over Standard of Care for Treatment of STS

GeDDiS Trial: Gemcitabine/Docetaxel Shows No Advantage over Standard of Care for Treatment of STS

Doxorubicin is currently the standard of care for first-line treatment for locally advanced or metastatic soft tissue sarcomas (STS). Phase II and retrospective study data suggest that the combination of gemcitabine and docetaxel may be effective in treating STS. Beatrice M. Seddon, MD, of the University College Hospital, United Kingdom, presented the results of the GeDDiS trial (Abstract 10500) during the Sarcoma Oral Abstract Session on Monday, June 1. This phase III, randomized, multicenter study compared the combination of gemcitabine and docetaxel with doxorubicin in patients with previously untreated advanced unresectable or metastatic STS.

Dr. Beatrice M. Seddon

The study was conducted at 24 centers in the United Kingdom and one center in Switzerland. Eligible patients were age 13 or older and had locally advanced or metastatic STS with histologic confirmation of high-grade disease and evidence of disease progression within the previous 6 months. Patients could not have received prior chemotherapy for sarcoma or doxorubicin for any previously treated cancer. In addition, study participants had measurable disease evaluable by RECIST 1.1, a performance status of 0-2, adequate organ function, and a life expectancy of at least 3 months.

Fig. 1. GeDDiS Trial Progression-Free Survival at 24 Weeks

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Fig. 1. GeDDiS Trial Progression-Free Survival at 24 Weeks

Patients were randomly assigned 1:1 to the control arm (75 mg/m2 of doxorubicin on day 1 every 21 days for six cycles) or the investigational arm (675 mg/m2 of gemcitabine on days 1 and 8 plus 75 mg/m2 of docetaxel on day 8 every 21 days for six cycles with granulocyte colony-stimulating factor). The randomization was stratified by age (18 or younger or over 18) and histologic subtype (uterine leiomyosarcoma, synovial sarcoma, pleomorphic, or other types of eligible STS). The primary endpoint was the proportion of patients who were progression-free at 24 weeks.

A total of 257 patients were enrolled—129 patients were randomly assigned to doxorubicin treatment, and 128 patients were randomly assigned to the investigational arm. Three patients did not receive treatment.

The median follow-up was 19 months. Approximately 60% were women, with a median age of 55 years. Patients in the investigational arm had lower dose intensity (83.3% vs. 94.6% for doxorubicin), more dose delays (55.5% vs. 45.7% for doxorubicin), and more withdrawals because of unacceptable toxicity (10.2% vs. 0.8% for doxorubicin).

In the doxorubicin group, 46.1% of patients were progression-free at 24 weeks compared with 46.0% of patients in the gemcitabine plus docetaxel arm, resulting in an unadjusted hazard ratio (HR) of 1.28 (95% CI [0.98, 1.67]; p = 0.07; Fig.1). Overall survival at 24 weeks was 86.7% for doxorubicin and 82.5% for gemcitabine plus docetaxel (unadjusted HR 1.07, 95% CI [0.77, 1.49]; p = 0.67). Dr. Seddon concluded that doxorubicin should remain standard of care for first-line treatment for patients with metastatic or locally advanced STS.

In his overview of the GeDDiS study, discussant Laurence H. Baker, DO, of the University of Michigan, called upon the sarcoma research community to agree on standard criteria for trials of this nature to accelerate the delivery of better therapies for patients with STS.

Watch the session: Visit the ASCO Virtual Meeting website.