olaratumab

Action and Spectrum

Action:
Olaratumab is a human monoclonal antibody that specifically targets platelet-derived growth factor receptor alpha (PDGFR-α), a receptor involved in cell growth, survival, and angiogenesis. By binding to PDGFR-α, olaratumab blocks its activation by natural ligands (PDGF), inhibiting downstream signaling pathways that promote tumor cell proliferation and survival. This blockade helps to slow or stop the growth of certain tumors driven by PDGFR-α. 

Spectrum:
Olaratumab is primarily used in the treatment of soft tissue sarcoma (STS), especially in combination with doxorubicin for advanced or metastatic cases. Its effectiveness is linked to tumors that express PDGFR-α or are dependent on PDGF signaling for growth. 

Drug Interaction

Adverse Reaction

Adverse drug reactions:   

Frequency defined   

>10%   

Lymphopenia   

Nausea   

Fatigue   

Neutropenia   

Musculoskeletal pain   

Thrombocytopenia   

Mucositis   

Alopecia   

Hyperglycemia   

Hypokalemia   

Hypophosphatemia   

Headache   

Increased alkaline phosphatase   

Hypomagnesemia   

Infusion-related reactions   

Anxiety   

Dry eyes   

1-10%   

Fatigue   

Musculoskeletal pain   

Hypokalemia    

Increases aPTT   

Abdominal pain   

Black Box Warning

None

Contraindication / Caution

Contraindications 

Known hypersensitivity to olaratumab or any of its components. 

Cautions 

Cardiac toxicity 

Hemorrhage 

Impaired wound healing 

Pregnancy and Lactation 

Pregnancy / Lactation

Pregnancy warnings:    

• US FDA pregnancy category: not assigned 

Breastfeeding warnings: 

• The release of the drug into the human breastmilk is unknown  

Pregnancy Categories:      

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first trimester or the later trimester      
• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women      
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a result in humans must take care of potential risks in pregnant women      
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits      
• Category X: Drugs listed in this category outweigh risks over benefits Hence these categories of drugs need to be avoided by pregnant women      
• Category N: There is no data available for the drug under this category     

Pharmacology

Olaratumab is a fully human monoclonal antibody that selectively binds to the platelet-derived growth factor receptor alpha (PDGFR-α). By blocking PDGFR-α activation, olaratumab inhibits downstream signaling pathways responsible for cell proliferation, survival, and angiogenesis. This targeted inhibition disrupts tumor growth and the tumor microenvironment, particularly in cancers dependent on PDGF signaling, such as soft tissue sarcoma. 

Pharmacodynamics 

Olaratumab binds specifically to the platelet-derived growth factor receptor alpha (PDGFR-α) on the surface of tumor and stromal cells. This binding blocks the receptor’s interaction with its natural ligands, preventing receptor activation and downstream signaling that promotes cell proliferation, survival, and angiogenesis. By inhibiting PDGFR-α signaling, olaratumab slows tumor growth and disrupts the supportive tumor microenvironment. This contributes to its anti-cancer effects, especially when used in combination with chemotherapy. 

Pharmacokinetics 

Absorption 

Administered intravenously, ensuring complete bioavailability. 

Distribution 

The volume of distribution is 7.7 L. 

Metabolism 

Degraded by proteolytic enzymes into small peptides and amino acids, as typical for monoclonal antibodies. 

Excretion and Elimination:  

The rate of clearance is 0.56 L/day. 

The terminal half-life is approximately 11 days. 

Adminstartion

Olaratumab is given by intravenous infusion over approximately 60 minutes. The infusion should be delivered through a dedicated IV line using a sterile, nonpyrogenic, low-protein-binding filter. Patients should be monitored during and after the infusion for any signs of infusion-related reactions, and appropriate premedication or interventions should be available if needed. 

Patient Information Leaflet

Generic Name: olaratumab 

Pronounced: oh-lar-At-ue-mab 

Why do we use olaratumab?  

Olaratumab is primarily used in combination with doxorubicin for the treatment of advanced or metastatic soft tissue sarcoma (STS). It is intended for patients whose tumors are not amenable to curative treatment with surgery or radiation. By targeting PDGFR-α, olaratumab helps to inhibit tumor growth and improve outcomes when combined with chemotherapy in this aggressive type of cancer.