Olaratumab

Medical uses

Olaratumab is used in combination with doxorubicin for the treatment of adults with advanced soft-tissue sarcoma (STS) who cannot be cured by cancer surgery or radiation therapy, and who have not been previously treated with doxorubicin.

In a randomised controlled trial with 133 STS patients, olaratumab plus doxorubicin improved the median of progression-free survival from 4.1 to 6.6 months as compared to doxorubicin alone (p = 0.0615, narrowly missing statistical significance), and overall survival from 14.7 to 26.5 months (p = 0.0003, highly significant).

Contraindications

The drug has no contraindications apart from hypersensitivity reactions.

Side effects

In studies, the most serious side effects of the combination olaratumab/doxorubicin were neutropenia (low count of neutrophil white blood cells) with a severity of grade 3 or 4 in 55% of patients, and musculoskeletal pain grade 3 or 4 in 8% of patients. Common milder side effects were lymphopenia, headache, diarrhoea, nausea and vomiting, mucositis, and reactions at the infusion site; all typical effects of cancer therapies.

Interactions

No pharmacokinetic interactions with doxorubicin were observed in studies. Being a monoclonal antibody, olaratumab is neither metabolised by cytochrome P450 liver enzymes nor transported by transmembrane pumps, and is thus not expected to interact relevantly with other drugs.

Mechanis of action

Olaratumab inhibits growth of tumour cells by blocking subunit alpha of the platelet-derived growth factor receptor, a type of tyrosine kinase.

Pharmacokinetics

After intravenous infusion, olaratumab has a volume of distribution of 7.7 litres in steady state and a biological half-life of 11 days.

History

Olaratumab was originally developed by ImClone Systems, which was acquired by Eli Lilly in 2008. A Phase I clinical trial was conducted in Japanes patients in September 2010, followed by a Phase II trial in 133 patients, starting in October 2010.

In February 2015, the European Medicines Agency assigned olaratumab orphan drug status for the treatment of soft-tissue sarcoma. The European Commission granted a conditional marketing authorisation, based on the mentioned Phase II study, valid throughout the European Union on 9 November 2016.

Considered a promising drug, the FDA granted olaratumab fast track designation, breakthrough therapy designation and priority review status. In October 2016, the US FDA issued an accelerated approval notice for use of olaratumab with doxorubicin to treat adults with certain types of soft-tissue sarcoma, based on the same study.

A Phase III trial started in September 2015 and is expected to complete in September 2020.