Olaratumab (Lartruvo, Lilly) for the treatment of soft tissue sarcoma is currently being studied by the European Parliament Committee for Medicinal Products for Human Use (CHMP) and the United States Food and Drug Administration (FDA), after the recent announcement of the results of a confirmatory study, has not been shown to demonstrate a profit in terms of survival.
Both agencies say that no new patient with soft tissue sarcoma should be initiated on olaratumab.
In addition, the manufacturer said that he had suspended his product promotion.
Olaratumab is a monoclonal antibody to platelet derived growth factor alpha receptor (PDGFR-α).
The drug has been available in Europe and the United States since 2016 and has been used in combination with doxorubicin in the treatment of patients with advanced soft tissue sarcoma who can not be treated with curative treatment by surgery or radiotherapy and who have never been treated with doxorubicin.
The product has received conditional approval from the European Medicines Agency as well as an accelerated approval from the FDA.
These approvals are based on the results of a Phase 2 trial in 133 patients with soft tissue sarcoma, published in 2016 at The lancet .
This trial showed better results with the combination of olaratumab and doxorubicin compared with doxorubicin alone. Median progression-free survival was improved from 4.1 to 6.6 months with olaratumab and doxorubicin (P = .0615, which just missed being statistically significant). Median overall survival increased from 14.7 to 26.5 months with the combination of the two drugs (P = 0.0003, which was highly significant).
Confirmation test is negative
However, both agencies requested that the manufacturer conduct a confirmatory test.
Lilly has recently announced that the results of this confirmatory test were negative.
This was the trial phase 3 ANNOUNCE, which revealed no benefit in terms of survival following the addition of olaratumab to doxorubicin, compared to treatment by doxorubicin alone.
"Lilly is working with global regulators to determine the next appropriate steps," the manufacturer said in a press release.
"As these discussions continue, patients currently receiving olaratumab can, in consultation with their physician, continue their treatment if they get clinical benefits," commented Lilly. For patients who have not yet received the product, the results of the Phase 3 trial do not support the initiation of treatment, apart from participation in a clinical trial, added the company.
ADVERTISING Details of the test
Lilly also gives some details about the ANNOUNCE trial in his 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 (undisclosed number) with locally advanced soft tissue sarcoma, unresectable or metastatic that could not be treated with curative treatment. They could have been treated previously with any number of treatments, but not with doxorubicin or another anthracycline.
The trial compared a combination therapy with olaratumab and doxorubicin, followed by treatment with olaratumab as monotherapy, versus doxorubicin and placebo, and then a placebo.
The results show that the association did not improve the overall survival of the study population nor the subgroup of patients with leiomyosarcoma, the company said.
No new safety signals were identified and the safety profile was comparable between treatment groups, Lilly adds.