Early Results Find Olaratumab Combo With Doxorubicin Plus Ifosfamide Safe
Initial results of the phase 1b study of olaratumab plus doxorubicin and ifosfamide have shown the combination to be safe, reported Sebastian Bauer, MD, of the West German Cancer Center, University of Duisburg-Essen, Essen, Germany, and his colleagues at CTOS 2018.
The phase 1 trial (NCT03283696) enrolled 16 patients with advanced or metastatic soft tissue sarcomas. Patients had received no prior lines of systemic therapy and had an ECOG performance status of 0-1. Adequate follow-up data were available for 10 patients.
Olaratumab (Lartruvo), which binds platelet-derived growth factor receptor alpha (PDGFRα), was given at 15 mg/kg in combination with doxorubicin (75 mg/m2 on days 1-3) and ifosfamide (10 g/m2 on days 1-4). This was followed by mandatory granulocyte-colony-stimulating factor therapy in cycles 1-6 on a 21-day cycle. Doxorubicin could be administered by continuous infusion or bolus administration and with cardiac protection. Mesna dosing was at least 60% of the ifosfamide dose.
Two of the 10 patients had dose-limiting toxicities; one had grade 4 febrile neutropenia and the other had grade 3 febrile neutropenia and grade 3 mucositis. Common related adverse events occurring in over 30% of patients included fatigue, anemia, neutropenia, thrombocytopenia, constipation, and nausea. One patient discontinued study treatment due to progressive disease, and all others were on study treatment as of the data cutoff. Among 7 patients evaluated for tumor response, 3 patients had a partial response according to RECIST and 3 other patients had stabilized disease as best overall response, for a disease control rate of 86%.
Given that 8 of 10 evaluable patients have completed the dose-limiting toxicity period without dose-limiting toxicities at the 15 mg/kg dose level of olaratumab, the study has proceeded to the next cohort. In those patients, an olaratumab loading dose of 20 mg/kg will be evaluated in cycle 1, followed by 15 mg/kg of olaratumab in subsequent cycles with the same doses of doxorubicin plus ifosfamide, the researchers wrote in their abstract.
NOTE: Since CTOS 2018, olaratumab plus doxorubicin did not meet its phase 3 endpoint of overall survival (OS) advantage in the full study population or in the leiomyosarcoma subpopulation compared to doxorubicin alone.