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Updated: Nov 30, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Circulating Tumor Cells and Biomarker Modulation with Olaratumab Monotherapy Followed by Olaratumab plus Doxorubicin:
Javier Martín-Broto1, Antonio López Pousa2, Andrew S Brohl3
1University Hospital Virgen del Rocio/Institute of Biomedicine of Seville, Seville, Spain.
Abstract:
This phase Ib study enumerated whole blood circulating tumor cells (CTC) and evaluated biomarkers in patients with potentially resectable soft-tissue sarcoma (STS) treated with olaratumab monotherapy (20 mg/kg) for one cycle followed by up to six cycles of olaratumab (20 mg/kg, cycles 1-2; 15 mg/kg, cycles 3-7) plus doxorubicin (75 mg/m2 on day 1). CTCs, platelet-derived growth factor receptors (PDGFR), and PDGF ligand expression in tumor tissue pre- and post-olaratumab monotherapy were evaluated. Antitumor activity, safety, pharmacokinetics, and PET/biomarker association with clinical outcome were assessed. Of 51 treated patients, 35, 43, and 37 were evaluable for CTC enumeration, PDGFRs, and PDGF ligand expression, respectively. An increase in CTCs at cycle 1 day 8 was observed, followed by a significant reduction by cycle 3 day 1 or 30-day follow-up. Decrease in CTC counts after olaratumab monotherapy was higher in patients with disease control than without disease control (57.9% vs. 31.2%). Baseline IHC expression was positive in most patients for PDGFRα [n = 31 (72.1%)] and PDGFRβ [n = 36 (83.7%)]. Similar rates were observed post-olaratumab monotherapy [PDGFRα, n = 30 (69.8%); PDGFRβ, n = 33 (76.7%)]. Eleven patients (29.7%) showed a 30% reduction by RT-PCR in PDGFRα at cycle 2. PDGFR expression and PET response showed no correlation with clinical outcome. Safety and pharmacokinetic profiles were consistent with previous reports. This study, the first to use a validated method for CTC detection, confirms that CTC enumeration in STS is feasible. However, no correlation was observed between PDGFRα expression and clinical outcome.
Insights
This study found that counting circulating tumor cells (CTCs) in soft-tissue sarcoma (STS) patients is feasible. While CTCs decreased after olaratumab treatment, their levels did not correlate with clinical outcomes or PDGFR expression.
Area of Science:
- Oncology
- Pharmacology
- Biomarker Research
Background:
- Soft-tissue sarcoma (STS) is a rare malignancy.
- Olaratumab, a platelet-derived growth factor receptor (PDGFR) inhibitor, has shown potential in STS treatment.
- Evaluating circulating tumor cells (CTCs) and biomarkers may offer insights into treatment response.
Purpose of the Study:
- To assess the feasibility of enumerating CTCs in patients with potentially resectable STS.
- To evaluate the association of CTCs, PDGFR expression, and other biomarkers with clinical outcomes.
- To assess the safety and pharmacokinetics of olaratumab-based therapy.
Main Methods:
- Phase Ib study involving patients with potentially resectable STS treated with olaratumab monotherapy followed by olaratumab plus doxorubicin.
- Enumeration of whole blood CTCs and evaluation of PDGFR and PDGF ligand expression in tumor tissue pre- and post-treatment.
- Assessment of antitumor activity, safety, pharmacokinetics, and PET/biomarker associations with clinical outcome.
Main Results:
- CTC enumeration was feasible in STS patients.
- An initial increase in CTCs was followed by a significant reduction after olaratumab monotherapy, with greater reduction in patients achieving disease control.
- PDGFRα and PDGFRβ expression was common, but PDGFRα expression did not correlate with clinical outcome; PET response also showed no correlation.
Conclusions:
- CTC enumeration is a feasible method for monitoring STS patients.
- While CTCs decrease with olaratumab treatment, their levels do not predict clinical outcomes in this study.
- PDGFR expression and PET response were not correlated with clinical outcomes, suggesting further research is needed for predictive biomarkers.
