We were presenting the final results of a clinical trial known as ANNOUNCE which was actually a phase III clinical trial which was comparing a drug called olaratumab in combination with doxorubicin versus doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma.
Would you be able to go through the methods that you used?
Sure, the study was an important study because in 2010 there was a phase Ib/II clinical trial which was actually looking at the same population, so advanced or metastatic soft tissue sarcoma, and was a proof of principle clinical trial. We actually compared olaratumab and doxorubicin to doxorubicin alone. What happened was there was a tremendous improvement in overall survival for the combination over single agent doxorubicin and based on that study the FDA eventually gave accelerated approval in 2016 for olaratumab. Today we’re actually presenting the results of the follow-up study which is the large randomised placebo-controlled phase III study to actually see if we could validate the results that we saw in the phase II.
The study was important because olaratumab with doxorubicin actually gained widespread use in over forty countries worldwide. Unfortunately, when we looked at the data from the phase III trial overall survival was not improved for the combination over the combination of doxorubicin and placebo. So the results did not confirm the findings that we had in the phase II study. Because of this olaratumab is actually being withdrawn from the market. So it was surprising results and the sarcoma community is trying very much to understand why there were such disparate results between the clinical trials.
Sarcoma actually represents a heterogeneous group of really rare malignancies, some say about 50-80 different subtypes. What we now know about those subtypes is they are different cancers, many of which have different biologies. So there’s a lot of thought that lumping a lot of these subtypes together could have actually skewed the results. There were also some differences between the phase II clinical trial and the phase III clinical trial such as the phase II clinical trial was a smaller study, it was an unblinded study, there was no placebo. Because of that and the heterogeneity of the populations we’re wondering if that’s why we saw some of the differences between the two clinical trials.
What were the main conclusions that you found?
The main conclusion right now is that olaratumab may not have activity in soft tissue sarcoma. So the practice-changing results will be that the drug will be removed from the market. We’re not recommending that any new patients start the drug if they need it, or it’s thought that they need it, and patients who are on it but are perceived to be having clinical benefit with informed discussions with their clinician they can get the drug and continue on through a patient access programme that is being set up.