Advice for healthcare professionals:
- the ANNOUNCE phase 3 study (an EU regulatory requirement) to assess olaratumab (Lartruvo▼) in combination with doxorubicin in patients with advanced or metastatic soft tissue sarcoma failed to show a clinical benefit
- the benefit-risk balance of olaratumab is therefore negative and the marketing authorisation in the EU will be withdrawn
- do not start new patients on olaratumab
- for patients currently on treatment, consider alternative treatment options since available stock will expire by April 2020
- continue to report any suspected adverse reactions to black triangle medicines to the Yellow Card Scheme
Olaratumab was authorised in the European Union in November 2016 to treat advanced soft tissue sarcoma. At time of its approval, data on the effects of olaratumab were limited due to the small number of patients included in the main study that supported the conditional authorisation as an orphan drug. The medicine was therefore granted a marketing authorisation on condition that the company provided additional data from the ANNOUNCE study (ClinicalTrials.gov identifier NCT02451943) to confirm the efficacy and safety of the medicine.
ANNOUCE study findings
The ANNOUNCE study did not show clinical benefit of olaratumab in combination with doxorubicin compared with doxorubicin, a standard of care treatment for advanced soft tissue sarcoma. Specifically, the study of 509 patients (258 in the investigational arm and 251 in the control arm) did not meet the primary endpoint to prolong overall survival in the study (hazard ratio 1.05; 95% CI 0.84–1.30; median overall survival 20.4 months for the olaratumab plus doxorubicin group versus 19.8 months for the doxorubicin group).
Overall survival was also not prolonged by olaratumab in the subpopulation of 234 patients with leiomyosarcoma (119 in the investigational arm and 115 in the control arm; hazard ratio 0.95, 95% CI 0.690–1.312; median overall survival 21.6 months for the olaratumab plus doxorubicin group versus 21.9 months for the doxorubicin group).
There was no clinical benefit for key secondary efficacy endpoints, including median progression-free survival in the overall population (hazard ratio 1.23, 95% CI 1.009–1.502; median progression-free survival 5.4 months for the olaratumab plus doxorubicin group versus 6.8 months for the doxorubicin group).
No new safety concerns were identified in the study.
Because this study did not show a clinical benefit, the conditional marketing authorisation for olaratumab will be withdrawn.
Report suspected adverse drug reactions via the Yellow Card Scheme
Please continue to report any suspected adverse drug reaction via the Yellow Card Scheme, even if the suspect drug no longer has a marketing authorisation.
Healthcare professionals, patients, and caregivers can report suspected side effects via the Yellow Card website or via the Yellow Card App available from Apple App Store and Google Play Store.
You can also use the app to access the latest safety information from the MHRA about medicines and medical devices on the Newsfeed. Search for medicines to see details of Yellow Card reports others have made. Medicines of interest to you can also be added to a Watch List to receive news and alerts about new side effects and safety advice as it emerges.
Letter sent to healthcare professionals. May 2019.
Article citation: Drug Safety Update volume 12, issue 11: June 2019: 3.