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Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas

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...

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Autores principales: Attia, Steven, Villalobos, Victor, Hindi, Nadia, Wagner, Andrew J., Chmielowski, Bartosz, Oakley, Gerard J., Peterson, Patrick M., Ceccarelli, Matteo, Jones, Robin L., Dickson, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572019/
https://www.ncbi.nlm.nih.gov/pubmed/37835565
http://dx.doi.org/10.3390/cancers15194871
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author Attia, Steven
Villalobos, Victor
Hindi, Nadia
Wagner, Andrew J.
Chmielowski, Bartosz
Oakley, Gerard J.
Peterson, Patrick M.
Ceccarelli, Matteo
Jones, Robin L.
Dickson, Mark A.
author_facet Attia, Steven
Villalobos, Victor
Hindi, Nadia
Wagner, Andrew J.
Chmielowski, Bartosz
Oakley, Gerard J.
Peterson, Patrick M.
Ceccarelli, Matteo
Jones, Robin L.
Dickson, Mark A.
author_sort Attia, Steven
collection PubMed
description 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/m(2), Days 1 and 8), and docetaxel (75 mg/m(2), 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.
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spelling pubmed-105720192023-10-14 Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas Attia, Steven Villalobos, Victor Hindi, Nadia Wagner, Andrew J. Chmielowski, Bartosz Oakley, Gerard J. Peterson, Patrick M. Ceccarelli, Matteo Jones, Robin L. Dickson, Mark A. Cancers (Basel) Article 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/m(2), Days 1 and 8), and docetaxel (75 mg/m(2), 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. MDPI 2023-10-06 /pmc/articles/PMC10572019/ /pubmed/37835565 http://dx.doi.org/10.3390/cancers15194871 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Attia, Steven
Villalobos, Victor
Hindi, Nadia
Wagner, Andrew J.
Chmielowski, Bartosz
Oakley, Gerard J.
Peterson, Patrick M.
Ceccarelli, Matteo
Jones, Robin L.
Dickson, Mark A.
Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas
title Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas
title_full Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas
title_fullStr Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas
title_full_unstemmed Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas
title_short Randomized Phase 2 Clinical Trial of Olaratumab in Combination with Gemcitabine and Docetaxel in Advanced Soft Tissue Sarcomas
title_sort randomized phase 2 clinical trial of olaratumab in combination with gemcitabine and docetaxel in advanced soft tissue sarcomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572019/
https://www.ncbi.nlm.nih.gov/pubmed/37835565
http://dx.doi.org/10.3390/cancers15194871
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