Olaratumab in soft tissue sarcoma - Current status and future perspectives.
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Date
2018-03-01Author
Antoniou, G
Lee, ATJ
Huang, PH
Jones, RL
Type
Journal Article
Metadata
Show full item recordAbstract
Recent randomised phase II trial data have indicated that the addition of olaratumab, a novel monoclonal antibody against platelet-derived growth factor receptor alpha (PDGFRα), to doxorubicin confers an unprecedented improvement in overall survival to patients with anthracycline-naïve advanced soft tissue sarcoma. However, this result was disproportionate with progression-free survival and response rate, and consequently there are unanswered questions regarding the precise mechanism of action of olaratumab. While preclinical data show that olaratumab specifically inhibits PDGFRα-mediated oncogenic signalling with attendant anti-tumour effects, a lack of correlation between pharmacodynamics markers of PDGFRα inhibition and clinical benefit from olaratumab suggest other mechanisms beyond modulation of downstream PDGFRα molecular pathways. Proposed mechanisms of olaratumab activity include engagement of anti-tumour immune responses and alterations of the tumour stroma, but these require further evaluation. Meanwhile, the drug-specific contribution of cytotoxic agents to olaratumab-containing combinations has yet to be characterised. Ongoing and future preclinical and translational studies, coupled with the anticipated results of a phase III trial that has completed enrolment, should provide greater insight into the efficacy and mode of action of olaratumab in soft tissue sarcomas.
Collections
Subject
Animals
Humans
Sarcoma
Soft Tissue Neoplasms
Disease Progression
Receptor, Platelet-Derived Growth Factor alpha
Antineoplastic Agents
Antibodies, Monoclonal
Disease-Free Survival
Treatment Outcome
Signal Transduction
Molecular Targeted Therapy
Biomarkers, Tumor
Research team
Sarcoma Clinical Trials (R Jones)
Molecular and Systems Oncology
Language
eng
Date accepted
2017-12-25
License start date
2018-03
Citation
European journal of cancer (Oxford, England : 1990), 2018, 92 pp. 33 - 39
Publisher
ELSEVIER SCI LTD