FDA Grants Priority Review to Olaratumab for Advanced Soft-Tissue Sarcoma

The US Food and Drug Administration (FDA) has granted a priority review to olaratumab (Eli Lilly), in combination with doxorubicin, for the treatment of soft-tissue sarcoma. The review is specifically in soft-tissue sarcoma patients who are not candidates for curative treatment with radiotherapy or surgery.

Olaratumab is a human anti–platelet-derived growth factor α (PDGFRα) monoclonal antibody; PDGFRα is overexpressed in various tumor types including soft-tissue sarcoma.

The priority review, which means the FDA aims to take action on the drug’s approval application within 6 months instead of the standard 10, was granted based on results of a phase II trial that were presented last June at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

In that trial, 133 patients with unresectable/metastatic soft-tissue sarcoma were randomized to either doxorubicin in combination with olaratumab or doxorubicin alone; the doxorubicin alone patients were permitted to cross over and receive olaratumab at the point of progression.

The median progression-free survival was 6.6 months in the combination group and 4.1 months in the monotherapy group, for a hazard ratio (HR) of 0.672 (95% CI, 0.442–1.021; P = .0615).

An interim overall survival analysis showed substantial improvement with the combination therapy. Those treated with olaratumab had a median overall survival of 25 months, compared with 14.7 months in the monotherapy group, for an HR of 0.44 (P = .0005). The objective response rates did not differ significantly between the two arms. The lead author of that study, William D. Tap, MD, of Memorial Sloan Kettering Cancer Center in New York, said at ASCO that this was the first time an agent added to doxorubicin improved overall survival in this malignancy.

Grade 3 or higher adverse events that occurred in more combination therapy patients than monotherapy patients included neutropenia, anemia, fatigue, and thrombocytopenia.

Based on these results, a phase III trial of the combination therapy was initiated, and is currently recruiting patients. The trial will eventually include an estimated 460 soft-tissue sarcoma patients.

"We are hopeful that, if approved, olaratumab will provide a meaningful addition to the limited treatment options for this rare and difficult-to-treat disease,” said Richard Gaynor, MD, senior vice president of Eli Lilly, in a press release.