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Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue
Steven Attia1, Victor Villalobos2, Nadia Hindi3,4,5
1Mayo Clinic, Jacksonville, FL 32224, USA.
Abstract:
Gemcitabine plus docetaxel is an effective treatment regimen for advanced soft tissue sarcomas (STSs). However, the prognosis for patients remains poor, and thus there is an urgent medical need for novel and effective therapies to improve long-term outcomes. The aim of the ANNOUNCE 2 trial was to explore the addition of olaratumab (O) to gemcitabine (G) and docetaxel (D) for advanced STS. Adults with unresectable locally advanced/metastatic STS, ≤2 prior lines of systemic therapy, and ECOG PS 0-1 were eligible. In Phase 2, patients were randomized 1:1 from two cohorts (O-naïve and O-pretreated) to 21-day cycles of olaratumab (20 mg/kg Cycle 1 and 15 mg/kg other cycles, Days 1 and 8), gemcitabine (900 mg/m2, Days 1 and 8), and docetaxel (75 mg/m2, Day 8). The primary objective was overall survival (OS) in the O-naïve population (α level = 0.20). Secondary endpoints included OS (O-pretreated), other efficacy parameters, patient-reported outcomes, safety, pharmacokinetics, and immunogenicity. A total of 167 and 89 patients were enrolled in the O-naïve and O-pretreated cohorts, respectively. Baseline patient characteristics were well balanced. No statistically significant difference in OS was observed between the investigational vs. control arm for either cohort (O-naïve cohort: HR = 0.95 (95% CI: 0.64-1.40), p = 0.78, median OS, 16.8 vs. 18.0 months; O-pretreated cohort: HR = 0.67 (95% CI: 0.39-1.16), p = 0.15, median OS 19.8 vs. 17.3 months). Safety was manageable across treatment arms. There was no statistically significant difference in the primary endpoint of OS between the two arms in the O-naïve population, and therefore based on hierarchical evaluation no other outcomes in this study can be considered statistically significant. No new safety signals were observed.
Insights
The ANNOUNCE 2 trial investigated adding olaratumab to gemcitabine and docetaxel for advanced soft tissue sarcomas. The combination did not significantly improve overall survival in either patient cohort.
Area of Science:
- Oncology
- Clinical Trials
- Soft Tissue Sarcomas
Background:
- Advanced soft tissue sarcomas (STSs) have a poor prognosis despite effective treatments like gemcitabine plus docetaxel.
- There is a critical need for novel therapies to improve long-term outcomes in advanced STS patients.
- The ANNOUNCE 2 trial aimed to evaluate olaratumab in combination with gemcitabine and docetaxel.
Purpose of the Study:
- To explore the efficacy and safety of adding olaratumab to gemcitabine and docetaxel in patients with advanced STSs.
- To assess overall survival (OS) as the primary endpoint in olaratumab-naïve patients.
- To evaluate secondary endpoints including OS in olaratumab-pretreated patients, safety, and patient-reported outcomes.
Main Methods:
- Phase 2 randomized trial enrolling adults with unresectable locally advanced/metastatic STS and limited prior therapy.
- Patients were randomized into two cohorts: olaratumab-naïve and olaratumab-pretreated.
- Treatment involved cycles of olaratumab, gemcitabine, and docetaxel, with OS as the primary endpoint in the olaratumab-naïve cohort.
Main Results:
- No statistically significant difference in overall survival was observed between the investigational and control arms in either the olaratumab-naïve (HR=0.95, p=0.78) or olaratumab-pretreated (HR=0.67, p=0.15) cohorts.
- Median OS was 16.8 months vs. 18.0 months for the olaratumab-naïve cohort and 19.8 months vs. 17.3 months for the olaratumab-pretreated cohort.
- The safety profile was manageable across all treatment arms, with no new safety signals identified.
Conclusions:
- The addition of olaratumab to gemcitabine and docetaxel did not result in a statistically significant improvement in overall survival for advanced STS patients.
- Based on the primary endpoint not being met, other outcomes were not considered statistically significant.
- The combination therapy demonstrated a manageable safety profile, but did not meet the primary efficacy objective.
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