The US Food and Drug Administration has granted accelerated approval to olaratumab (Lartruvo) in combination with doxorubicin for the treatment of patients with soft tissue sarcoma not amenable to curative therapy with radiation treatment or surgery and with a histologic subtype for which an anthracycline-containing regimen is appropriate.
Approval was based on finding from a clinical trial that compared olaratumab plus doxorubicin with doxorubicin alone in 133 patients with metastatic soft tissue sarcoma. Of those, 65% had not received prior chemotherapy, excluding adjuvant and neoadjuvant therapy, 38% had leiomyosarcoma, 1.5% had synovial sarcoma, and 61% had other histologies.
Patients in the experimental arm received olaratumab 15 mg/kg intravenously on days 1 and 8 plus doxorubicin 75 mg/m2 intravenously on day 1 of each 21-day cycle for up to 8 cycles. Patients were permitted to receive dexrazoxane on cycles 5 to 7.
Results showed that treatment with olaratumab was associated with a significant 48% reduction in the risk of death compared with single-agent doxorubicin (hazard ratio [HR], 0.52; 95% CI, 0.34-0.79). Median overall survival was 26.5 months (95% CI, 20.9-31.7) with olaratumab plus doxorubicin vs 14.7 months (95% CI, 9.2-17.1) with doxorubicin.
However, there was no significant difference in the risk of progression or death between the 2 treatment arms (HR, 0.74; 95% CI, 0.46-1.19), with a median progression-free survival of 8.2 months (95% CI, 5.5-9.8) and 4.4 months (95% CI, 3.1-7.4) for olaratumab and doxorubicin, respectively.
The most common adverse events associated with olaratumab treatment are nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache. Of note, 13% of patients experienced infusion-related reactions.
The recommended dose and schedule of olaratumab is 15 mg/kg intravenously over 60 minutes on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. Doxorubicin should be administered during the first 8 cycles of olaratumab.
Clinicians should premedicate patients with diphenhydramine and dexamethasone intravenously prior to olaratumab administration on day 1 of cycle 1.
1. Olaratumab (Lartruvo). U.S. Food and Drug Administration Approved Drugs website. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm526087.htm. October 19, 2016. Accessed October 21, 2016.