Olaratumab for Sarcoma Under Review After Negative Trial

Zosia Chustecka

February 01, 2019

Olaratumab (Lartruvo, Lilly) for the treatment of soft tissue sarcoma is now under review by the European Committee for Medicinal Products for Human Use (CHMP) and the US Food and Drug Administration (FDA) after recently announced results from a confirmatory study failed to show a survival benefit.

Both agencies say that no new patients with soft tissue sarcoma should be started on olaratumab.

In addition, the manufacturer has said that it has suspended its promotion of the product.

Olaratumab is a monoclonal antibody directed against platelet-derived growth factor receptor alpha (PDGFR-α).

The drug has been available in both Europe and the US since 2016, and has been used in combination with doxorubicin in the treatment of patients with advanced soft tissue sarcoma not amenable to curative therapy with surgery or radiation, and who have not previously been treated with doxorubicin.

The product was granted a conditional approval by the European Medicines Agency, and also an accelerated approval from the FDA.

Those approvals were based on results from a phase 2 trial in 133 patients with soft tissue sarcoma, which was published in 2016 in The Lancet .

That trial showed better outcomes with the combination of olaratumab plus doxorubicin when compared to doxorubicin alone. Median progression-free survival was improved from 4.1 to 6.6 months with the combination of olaratumab plus doxorubicin (P = .0615, which just missed being statistically significant). Median overall survival improved from 14.7 to 26.5 months with the combination of the two drugs (P = .0003, which was highly significant).

Confirmatory Trial Is Negative

However, both agencies required that a confirmatory trial be carried out by the manufacturer.

Lilly has recently announced that the results of that confirmatory trial were negative.

This was the phase 3 ANNOUNCE trial, which found no survival advantage to adding olaratumab to doxorubicin, when compared to treatment with doxorubicin alone.

 "Lilly is working with global regulators to determine the appropriate next steps," the manufacturer said in a press release.

"While these discussions are ongoing, patients who are currently receiving olaratumab may, in consultation with their physician, continue their course of therapy if they are receiving clinical benefit," Lilly commented. For patients who have not previously received the product, the results of the Phase 3 trial do not support initiating treatment, outside of participation in a clinical trial, the company added.  

Another trial is still ongoing. This is a global phase 2 trial that is investigating olaratumab in combination with gemcitabine and docetaxel in patients with advanced soft tissue sarcoma.

ANNOUNCE Trial Details

Lilly also gives a few details about the ANNOUNCE trial in its press release, but notes that the full results will be presented at an upcoming medical conference and will be published in a medical journal.

The trial was conducted in patients (number not disclosed) with locally advanced, unresectable or metastatic soft tissue sarcoma not amenable to curative treatment. They could have been treated previously with any number of therapies, but not with doxorubicin or another anthracycline.

The trial compared treatment with a combination of olaratumab with doxorubicin, followed by olaratumab monotherapy, vs doxorubicin plus placebo followed by placebo.

The results show that the combination did not improve overall survival in either the full study population or in a subgroup of patients with leiomyosarcoma, the company notes.

There were no new safety signals identified and the safety profile was comparable between treatment groups, Lilly adds.

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