The FDA granted accelerated approval to olaratumab (Lartruvo) in combination with doxorubicin for the treatment of soft-tissue sarcomas that is not amenable to curative treatment with radiotherapy or with surgery and with a histologic subtype treatable with anthracycline-containing regimens.
The US Food and Drug Administration (FDA) granted accelerated approval to olaratumab (Lartruvo) in combination with doxorubicin for the treatment of soft-tissue sarcomas with a histologic subtype treatable with anthracycline-containing regimens and that is not amenable to curative treatment with radiotherapy or with surgery.
“For these patients, Lartruvo, added to doxorubicin, provides a new treatment option,” said Richard Pazdur, MD, director of the FDA’s Office of Hematology and Oncology Products, in a press release. “This is the first new therapy approved by the FDA for the initial treatment of soft-tissue sarcoma since doxorubicin’s approval more than 40 years ago.”
Olaratumab is a platelet-derived growth factor receptor alpha (PDGFR-Î±) blocking antibody. It binds PDGFR-Î± and prevents activation of the receptor; the agent was previously granted fast track designation, breakthrough therapy designation, and priority review status by the FDA.
The approval was based on results of the JGDG open-label randomized trial. The study included 133 patients with a variety of different soft-tissue sarcoma subtypes, and randomized patients to either olaratumab plus doxorubicin or doxorubicin monotherapy.
The median overall survival was 26.5 months with olaratumab, compared with only 14.7 months without it, for a hazard ratio (HR) of 0.52 (95% CI, 0.34–0.79; P < .05). Median progression-free survival was also numerically better, at 8.2 months with olaratumab compared with 4.4 months with doxorubicin alone (HR, 0.74 [95% CI, 0.46–1.19]); though this was not statistically significant, it did meet the study’s prespecified PFS goal.
The objective response rate was 18.2% with olaratumab and 7.5% with doxorubicin monotherapy.
The most common adverse events (AEs) with olaratumab include nausea, fatigue, musculoskeletal pain, mucositis, vomiting, diarrhea, and headache. In the study, 8% of olaratumab patients experienced an AE resulting in therapy discontinuation; the most common such AE was infusion-related reaction (3%). AEs leading to dose reductions occurred in 25% of patients (most commonly neutropenia, in 20%), and dose delays due to AEs occurred in 52%.
“Lartruvo represents an important step forward in soft-tissue sarcoma treatment,” said William D. Tap, MD, of Memorial Sloan Kettering Cancer Center in New York and lead investigator of the study that led to the drug’s approval, in a press release from the manufacturer. “We are pleased with this approval, which will provide patients with a treatment option that offers new hope in their battle against this difficult disease.”