Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas
by
, and
Steven Attia
1,*,
Victor Villalobos
2,
Nadia Hindi
3,4,5,
Andrew J. Wagner
6,7,
Bartosz Chmielowski
8,
Gerard J. Oakley III
9,
Patrick M. Peterson
9,
Matteo Ceccarelli
9,
Robin L. Jones
10
and
Mark A. Dickson
11,12 1
Mayo Clinic, Jacksonville, FL 32224, USA
2
School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA
3
Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain
4
Fundación Jiménez Díaz University Hospital, 28040 Madrid, Spain
5
Hospital General de Villalba, 28400 Madrid, Spain
6
Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
7
Harvard Medical School, Boston, MA 02115, USA
8
Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA 90024, USA
9
Eli Lilly and Company, Indianapolis, IN 46255, USA
10
Institute of Cancer Research, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
11
Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
12
Weill Cornell Medical College, New York, NY 10065, USA
*
Author to whom correspondence should be addressed.
Cancers 2023, 15(19), 4871; https://doi.org/10.3390/cancers15194871
Submission received: 29 July 2023
/
Revised: 23 August 2023
/
Accepted: 18 September 2023
/
Published: 6 October 2023
(This article belongs to the Special Issue Targeted Therapy in Sarcoma)
Simple Summary
Soft tissue sarcomas (STSs) are rare and highly heterogeneous tumors that are difficult to treat. Gemcitabine plus docetaxel is an effective treatment for advanced STS. 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. Patients were randomized 1:1 from two cohorts (O-naïve and O-pretreated) to 21-day cycles of olaratumab, gemcitabine, and docetaxel. A total of 167 and 89 patients were enrolled in the O-naïve and O-pretreated cohorts, respectively. There was no statistically significant difference in the primary endpoint of overall survival between the two arms in the O-naïve population. No new safety signals were observed.
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.
