FDA approves Lartruvo for soft tissue sarcoma
The FDA granted accelerated approval to olaratumab injection for use in combination with doxorubicin to treat adults with soft tissue sarcoma.
Olaratumab (Lartruvo, Eli Lilly) is the first monoclonal antibody approved to treat soft tissue sarcoma, and it is the first FDA–approved frontline therapy for soft tissue sarcoma in more than 40 years.
The agent is indicated for patients with a histologic subtype for which an anthracycline-containing regimen is appropriate, and which is not amenable to curative treatment with surgery or radiotherapy.
“The approval of olaratumab is based on an encouraging and positive study for patients, and represents progress in soft tissue sarcoma treatment,” Richard Gaynor, MD, senior vice president of product development and medical affairs at Lilly Oncology, said in a company-issued press release. “For the first time in four decades, we now have a combination regimen — olaratumab and doxorubicin — that offers progress over doxorubicin alone in the front-line setting by improving overall survival for people with soft tissue sarcoma.”
The FDA based its decision on results of the open-label, randomized, active-controlled JGDG trial (n = 133), which evaluated doxorubicin with or without olaratumab in patients with soft tissue sarcoma. All patients had a histologic subtype that was suitable for an anthracycline-containing regimen but not amenable to curative treatment with radiotherapy or surgery.
OS, PFS and objective response rate served as efficacy outcome measures.
Patients assigned the combination achieved significantly longer median OS (26.5 months vs. 14.7 months; HR = 0.52; 95% CI, 0.34-0.79). Patients assigned the combination also achieved longer median PFS (8.2 months vs. 4.4 months; HR = 0.74; 95% CI, 0.46-1.19) and a higher ORR (18.2% vs. 7.5%).
At the time of analysis, 39 patients (59%) assigned the combination and 52 patients (78%) assigned doxorubicin alone had died.
The most common adverse reactions among patients assigned the combination regimen included nausea (73% for combination vs. 52% for doxorubicin alone), fatigue (69% vs. 69%), musculoskeletal pain (64% vs. 25%), mucositis (53% vs. 35%), vomiting (45% vs. 19%), diarrhea (34% vs. 23%) and headache (20% vs. 9%).
The most common laboratory abnormalities among patients assigned the combination were lymphopenia (77% for combination vs. 73% for doxorubicin alone), neutropenia (65% vs. 63%), thrombocytopenia (63% vs. 44%), hyperglycemia (52% vs. 28%), elevated activated partial thromboplastin time (33% vs. 13%), hypokalemia (21% vs. 15%) and hypophosphatemia (21% vs. 7%).
Febrile neutropenia occurred in 13% of patients assigned the combination and 12% of those assigned doxorubicin alone.
Adverse reactions in the combination group led to treatment discontinuation in five patients (8%), dose reductions in 16 patients (25%) and dose delays in 33 patients (52%).
“Olaratumab represents an important step forward in soft tissue sarcoma treatment,” William D. Tap, MD, chief of sarcoma medical oncology services at Memorial Sloan Kettering Cancer Center and the principal investigator of the JGDG registration trial, said in the press release. “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.”