The European Commission has granted an accelerated approval to olaratumab in combination with doxorubicin as a frontline therapy for patients with advanced soft tissue sarcoma, making it the first new therapy for this indication in over 40 years.
Robin L. Jones, MD, MRCP
The European Commission has granted an accelerated approval to olaratumab (Lartruvo) in combination with doxorubicin as a frontline therapy for patients with advanced soft tissue sarcoma, making it the first new therapy for this indication in over 40 years.
The decision, which was preceded by a positive opinion from the Committee for Medicinal Products for Human Use, was based on findings from the phase II JGDG study, which showed an 11.8-month improvement in overall survival (OS) with the PDGFRα antagonist versus doxorubicin alone. The median OS was 26.5 months with the combination versus 14.7 months with doxorubicin alone (HR, 0.463; 95% CI, 0.301-0.710, P = .0003).
"Lartruvo, in combination with doxorubicin, has demonstrated improved overall survival compared to doxorubicin alone in advanced soft tissue sarcomas, and is a promising new agent in these tumors," one of the investigators of the JGDG trial, Robin L. Jones, BSc, MB, MRCP, MD, consultant medical oncologist and head of the Sarcoma Unit at The Royal Marsden and team leader at The Institute of Cancer Research, London, said in a statement.
In the open-label phase II JGDG study, 133 patients with advanced STS were randomized to olaratumab plus doxorubicin (n = 66) or doxorubicin alone (n = 67). Of those enrolled, 129 received at least 1 dose of treatment (64, olaratumab combination; 65, doxorubicin).
Patient characteristics were well balanced between the arms and all patients had not received prior treatment with an anthracycline before entering the study. Following the study, 67% of those in the olaratumab group received subsequent therapy compared with 49% of those in the doxorubicin alone arm.
The median age of patients in the combination arm was 58.5 years, and most had an ECOG performance status of 0 to 1 (94%). Eighty-eight percent of patients were positive for PDGFRα. Thirty-six percent and 40% of patients had leiomyosarcoma, in the combination and monotherapy arms, respectively. Other common histologies in the olaratumab and control arms, respectively, included undifferentiated pleomorphic sarcoma (15% vs 21%, respectively) and liposarcoma (12% vs 22%).
By blinded independent review, median progression-free survival (PFS) was 8.2 versus 4.4 months for the olaratumab combo and doxorubicin alone, respectively (HR, 0.67; 95% CI, 040-1.12; P = .1208). By investigator assessment, median PFS was 6.6 months with olaratumab plus doxorubicin compared with 4.1 months with doxorubicin alone (HR, 0.67; 95% CI, 0.44-1.02; P = .0615).
By independent assessment, the objective response rate was 18.2% in the combination arm versus 7.5% in the doxorubicin arm. The complete response (CR) rate to the olaratumab combination was 4.5% and the partial response rate was 13.6%. The CR rate was 1.5% in the doxorubicin arm.
The most commonly reported all-grade adverse events (AEs) in the olaratumab group versus chemotherapy, respectively, were nausea (73% vs 52%), 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 all-grade hematologic AEs were lymphopenia (77% vs 73%), neutropenia (65% vs 63%), thrombocytopenia (63% vs 44%), and hyperglycemia (52% vs 28%). Febrile neutropenia was experienced by 13% of patients treated with olaratumab versus 12% of those in the doxorubicin alone group.
"With this decision, Lartruvo is now approved for use in the EU, offering a new treatment option and new hope to soft tissue sarcoma patients in Europe," Sue Mahony, PhD, senior vice president and president of Lilly Oncology, the company developing olaratumab, said in a statement. "This news further reinforces Lilly's ongoing commitment toward these types of rare diseases and the patient populations that are affected around the globe."
As part of the accelerated approval program, Lilly will be required to provide results from the ongoing phase III ANNOUNCE trial to support a continued authorization. This study is comparing the olaratumab/doxorubicin combination with doxorubicin alone (NCT02451943).
Tap WD, Jones RL, Van Tine BA, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;388(10043):488-497.