| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | PDGF-R α |
| Clinical data | |
| Trade names | Lartruvo |
| Other names | IMC-3G3, LY-3012207 |
| AHFS/Drugs.com | Monograph |
| License data | |
| Routes of administration | Intravenous infusion |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Protein binding | None |
| Metabolism | Proteolytic enzymes |
| Eliminationhalf-life | 11 days |
| Identifiers | |
| CAS Number | |
| DrugBank |
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| ChemSpider |
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| UNII | |
| KEGG |
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| Chemical and physical data | |
| Formula | C6554H10076N1736O2048S40 |
| Molar mass | 147241.21 g·mol−1 |
 N Y (what is this?) (verify) | |
Olaratumab, sold under the brand nameLartruvo, is amonoclonal antibody medication developed byEli Lilly and Company for the treatment ofsolid tumors. It is directed against theplatelet-derived growth factor receptor alpha.[2]
It was removed from the United States and European Union markets in 2019, due to insufficient proof of its medical advantage (see below "Medical uses").
Olaratumab is used in combination withdoxorubicin for the treatment of adults with advancedsoft-tissue sarcoma (STS) who cannot be cured bycancer surgery orradiation therapy, and who have not been previously treated with doxorubicin.[3][4]
In arandomised controlled trial with 133 STS patients, olaratumab plus doxorubicin improved themedian ofprogression-free survival from 4.1 to 6.6 months as compared to doxorubicin alone (p = 0.0615, narrowly missingstatistical significance), and overall survival from 14.7 to 26.5 months (p = 0.0003, highly significant).[3][5]However, the ANNOUNCE phase 3 trial did not find any advantage in adding olaratumab to doxorubicin. Therefore, in January 2019, FDA and EMA decided to recommend against starting olaratumab for soft tissue sarcoma.[6] In April 2019 the European Medicines Agency explicitly requested the marketing authorisation of the medicine to be revoked.[7] Shortly afterwards the German Physician's Medicines Commission reported that olaratumab will be removed from the German market "in a few weeks" and asked doctors not to treat new patients with this drug outside of clinical trials.[8] Lilly subsequently voluntarily withdrew its approval in the United States.[9]
The drug has no contraindications apart fromhypersensitivity reactions.[3]
In studies, the most serious side effects of the combination olaratumab/doxorubicin wereneutropenia (low count ofneutrophil 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 werelymphopenia, headache, diarrhoea,nausea and vomiting,mucositis, and reactions at the infusion site;[3] all typical effects of cancer therapies.
Nopharmacokinetic interactions with doxorubicin were observed in studies. Being a monoclonal antibody, olaratumab is neither metabolised bycytochrome P450 liver enzymes nor transported bytransmembrane pumps, and is thus not expected to interact relevantly with other drugs.[3]
Olaratumab inhibits growth of tumour cells by blocking subunit alpha of theplatelet-derived growth factor receptor, a type oftyrosine kinase.[3]
Afterintravenous infusion, olaratumab has avolume of distribution of 7.7 litres in steady state and abiological half-life of 11 days.[3]
Olaratumab was originally developed byImClone Systems, which was acquired byEli Lilly in 2008.[10] APhase I clinical trial was conducted in Japanese patients in September 2010,[11] followed by a Phase II trial in 133 patients, starting in October 2010.[12]
In February 2015, theEuropean Medicines Agency assigned olaratumaborphan drug status for the treatment of soft-tissue sarcoma.[13] TheEuropean Commission granted a conditional marketing authorisation, based on the mentioned Phase II study, valid throughout theEuropean Union on 9 November 2016.[14]
Previously considered a promising drug, the FDA granted olaratumabfast track designation,breakthrough therapy designation andpriority review status.In October 2016, the USFDA issued anaccelerated approval notice for use of olaratumab with doxorubicin to treat adults with certain types of soft-tissue sarcoma, based on the same study.[4][15]
A phase III trial completed in 2019, and unfortunately showed no benefit from the addition of olaratumab to doxorubicin.[15][16] As noted above, these results led to withdrawal of approval in the United States and Europe.
