FDA Grants Accelerated Approval to Lartruvo for Soft Tissue Sarcoma

First new initial treatment of STS in more than 40 years

The FDA has granted accelerated approval to olaratumab (Lartruvo, Eli Lilly) with doxorubicin to treat adults with certain types of soft tissue sarcoma (STS), which are cancers that develop in muscles, fat, tendons, or other soft tissues. Olaratumab is approved for use with the FDA-approved chemotherapy drug doxorubicin for the treatment of patients with STS who cannot be cured with radiation or surgery and who have a type of STS for which an anthracycline (chemotherapy) is an appropriate treatment.

Olaratumab is a platelet-derived growth factor (PDGF) receptor-alpha blocking antibody. When stimulated, PDGF receptors cause tumor growth. Olaratumab is the first new therapy approved for the initial treatment of STS since doxorubicin’s approval more than 40 years ago.

The National Cancer Institute estimates that 12,310 new cases of STS and nearly 5,000 deaths are likely to occur from the disease in 2016. The most common treatment for STS that cannot be removed by surgery is doxorubicin alone or with other drugs.

The safety and efficacy of olaratumab were evaluated in a randomized study involving 133 patients with more than 25 different subtypes of metastatic STS. The patients received either olaratumab with doxorubicin or doxorubicin alone. Study endpoints included overall survival (OS), progression-free survival (PFS), and the overall response rate (ORR).

The patients treated with olaratumab and doxorubicin showed a statistically significant improvement in median OS compared with those given doxorubicin alone (26.5 months and 14.7 months, respectively). Patients who received olaratumab with doxorubicin had median PFS of 8.2 months compared with 4.4 months for the doxorubicin group. Tumor shrinkage was 18.2% for patients treated with olaratumab/doxorubicin and 7.5% for those treated with doxorubicin alone.

Olaratumab can have serious adverse effects, including infusion-related reactions and embryo-fetal harm. Infusion-related reactions include hypotension, pyrexia, chills, and rash. The most common adverse effects of treatment include nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache.

The FDA granted the olaratumab application a fast track designation, a breakthrough therapy designation, and priority review status because preliminary clinical evidence indicated that it may offer a substantial improvement in efficacy in the treatment of a serious or life-threatening disease or condition. The FDA approved olaratumab under the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease or condition based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.

Olaratumab also received an orphan drug designation, which provides incentives, such as tax credits, to assist and encourage the development of drugs intended to treat rare diseases.

Source: FDA; October 19, 2016.