Randomized phase 2 clinical trial of olaratumab in combination with gemcitabine and docetaxel in advanced soft tissue sarcomas Journal Article
| Authors: | Attia, S.; Villalobos, V.; Hindi, N.; Wagner, A. J.; Chmielowski, B.; Oakley, G. J. 3rd; Peterson, P. M.; Ceccarelli, M.; Jones, R. L.; Dickson, M. A. |
| Article Title: | Randomized phase 2 clinical trial of olaratumab in combination with gemcitabine and docetaxel in advanced soft tissue sarcomas |
| 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. © 2023 by the authors. |
| Keywords: | immunohistochemistry; adolescent; adult; cancer survival; controlled study; human tissue; treatment response; middle aged; major clinical study; overall survival; constipation; fatigue; neutropenia; area under the curve; cancer combination chemotherapy; cancer growth; diarrhea; drug efficacy; drug safety; gemcitabine; outcome assessment; cancer grading; cell proliferation; biological marker; gastrointestinal stromal tumor; edema; progression free survival; quality of life; phase 2 clinical trial; anemia; allergy; leukopenia; nausea; randomized controlled trial; thrombocytopenia; vomiting; clinical assessment; cohort analysis; histology; docetaxel; coughing; dyspnea; questionnaire; algorithm; multicenter study; soft tissue sarcoma; time to maximum plasma concentration; kaposi sarcoma; phase 1 clinical trial; leiomyosarcoma; double blind procedure; alopecia; infusion; platelet count; dysgeusia; programmed death 1 receptor; progression-free survival; musculoskeletal pain; patient-reported outcome; brief pain inventory; olaratumab; response evaluation criteria in solid tumors; human; male; female; article; medical dictionary for regulatory activities; loss of appetite; ecog performance status; efficacy parameters; soft tissue sarcomas |
| Journal Title: | Cancers |
| Volume: | 15 |
| Issue: | 19 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2023-10-01 |
| Start Page: | 4871 |
| Language: | English |
| DOI: | 10.3390/cancers15194871 |
| PROVIDER: | scopus |
| PMCID: | PMC10572019 |
| PUBMED: | 37835565 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
