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Olaratumab: A Novel Platelet-Derived Growth Factor Receptor α-Inhibitor for Advanced Soft Tissue Sarcoma
Benjamin J Andrick1, Arpita Gandhi2
11 Geisinger Medical Center, Danville, PA, USA.
Objective:
To review and summarize data on olaratumab, which was approved by the US Food and Drug Administration (FDA) in October 2016, in combination with doxorubicin, for the treatment of advanced soft tissue sarcoma.
Data Sources:
A literature search using PubMed was conducted using the search terms olaratumab, IMC-3G3, and advanced soft tissue sarcoma from January 2005 to June 2017.
Study Selection And Data Extraction:
The literature search was confined to human studies published in English. Trials of olaratumab for advanced soft tissue sarcomas were prioritized.
Data Synthesis:
Olaratumab is a human antiplatelet-derived growth factor receptor α monoclonal antibody. Its accelerated FDA approval was based on a phase II randomized trial of olaratumab plus doxorubicin (n = 66) versus doxorubicin monotherapy (n = 67) in patients with advanced soft tissue sarcoma. Olaratumab 15 mg/kg was administered intravenously (IV) on days 1 and 8 in combination with doxorubicin 75 mg/m2 IV on day 1 every 21 days for a total of 8 cycles compared to doxorubicin 75 mg/m2 IV monotherapy. The response rate was 18.2% with combination therapy versus 11.9% with monotherapy and median progression-free survival of 6.6 and 4.1 months, respectively. Additionally, overall survival was increased by 11.8 months in the olaratumab arm (26.5 months vs 14.7 months). Clinically relevant adverse effects in the olaratumab + doxorubicin arm included neutropenia (58%), mucositis (53%), nausea (73%), vomiting (45%), and diarrhea (34%).
Conclusion:
Olaratumab, in combination with doxorubicin, represents a novel treatment strategy for advanced soft tissue sarcoma and provides a significant survival advantage for this rare disease state with limited treatment options.
Insights
Olaratumab combined with doxorubicin significantly improves survival for advanced soft tissue sarcoma patients. This novel treatment offers a survival advantage in a rare disease with limited therapeutic options.
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced soft tissue sarcoma is a rare disease with limited treatment options.
- Olaratumab is a human antiplatelet-derived growth factor receptor α monoclonal antibody.
Purpose of the Study:
- To review and summarize data on olaratumab in combination with doxorubicin for advanced soft tissue sarcoma.
- To assess the efficacy and safety of olaratumab plus doxorubicin.
Main Methods:
- Literature search of PubMed (January 2005 to June 2017) using terms: olaratumab, IMC-3G3, advanced soft tissue sarcoma.
- Prioritization of human studies in English, focusing on trials for advanced soft tissue sarcomas.
- Analysis of a phase II randomized trial comparing olaratumab plus doxorubicin to doxorubicin monotherapy.
Main Results:
- The combination therapy showed a response rate of 18.2% versus 11.9% for monotherapy.
- Median progression-free survival was 6.6 months with combination therapy vs. 4.1 months with monotherapy.
- Overall survival increased by 11.8 months (26.5 months vs. 14.7 months) with olaratumab plus doxorubicin.
Conclusions:
- Olaratumab plus doxorubicin is a novel treatment strategy for advanced soft tissue sarcoma.
- This combination provides a significant survival advantage for patients with this rare disease.
- The treatment offers a valuable option for a patient population with limited therapeutic choices.
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