RT Journal Article
T1 Circulating Tumor Cells and Biomarker Modulation with Olaratumab Monotherapy Followed by Olaratumab plus Doxorubicin: Phase Ib Study in Patients with Soft-Tissue Sarcoma.
A1 Martin-Broto, Javier
A1 Lopez-Pousa, Antonio
A1 Brohl, Andrew S
A1 Van-Tine, Brian A
A1 Powers, Benjamin
A1 Stacchiotti, Silvia
A1 Blay, Jean-Yves
A1 Hu, James S
A1 Oakley, Gerard J
A1 Wang, Hong
A1 Szpurka, Anna M
A1 Levy, Donna E
A1 Mo, Gary
A1 Ceccarelli, Matteo
A1 Jones, Robin L
K1 Adult
K1 Biomarkers, Tumor
K1 Doxorubicin
K1 Humans
K1 Male
K1 Middle Aged
K1 Platelet-Derived Growth Factor
K1 Positron-Emission Tomography
K1 Receptor, Platelet-Derived Growth Factor beta
AB 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.
PB American Association for Cancer Research
YR 2020
FD 2020-11-11
LK http://hdl.handle.net/10668/16589
UL http://hdl.handle.net/10668/16589
LA en
NO Martín-Broto J, Pousa AL, Brohl AS, Van Tine BA, Powers B, Stacchiotti S, et al. Circulating Tumor Cells and Biomarker Modulation with Olaratumab Monotherapy Followed by Olaratumab plus Doxorubicin: Phase Ib Study in Patients with Soft-Tissue Sarcoma. Mol Cancer Ther. 2021 Jan;20(1):132-141.
DS RISalud
RD Jul 5, 2025