In a Late Breaking Abstract which surprised no one, the ANNOUNCE study confirmed there is no significant benefit of adding Olaratumab to Doxorubicin in advanced soft tissue sarcoma. The agent is already in the process of having its licence withdrawn by the EMA and is no longer being marketed by the drug company.
Initial marketing authorisation came from the Phase 1b/2 study published in the Lancet in 2016. The combined study recruited fewer than 150 patients with a heterogeneous group of tumours and subjected them to doxorubicin with or without olaratumab. Despite non-significant differences in response rates or progression free survival, the overall survival statistic appeared highly significantly in favour of the combination therapy. Although there were obvious and significant flaws in these data, the supposed overall survival benefit was deemed to be sufficient to permit marketing in the US and then Europe. A condition of the marketing authorisation was to conduct a confirmatory phase 3 study.
Unfortunately, patients with advanced soft tissue sarcomas – desperate for hope – have been badly advised to request this drug. The unsubtle interpretation of the Lancet study has created a flurry of demand despite the increased toxicity (and increased cost). Approvals were made by national bodies like the SMC, and the drug was paid for by the NHS.
ANNOUNCE has confirmed all the doubts about the drug. Overall survival was no better in the combination arm, and progression free survival may have been worse.
I find it difficult to express my anger about the way this drug has come to market – and been promoted to patients – without breaking confidentialities. Needless to say, I’m delighted the Olaratumab story has come to an end for now.