The addition of olaratumab to doxorubicin significantly improves median progression-free and overall survival in contrast with doxorubicin alone in patients with advanced soft-tissue sarcoma, a study published in The Lancet has shown.1
Investigators evaluated the safety and efficacy of olaratumab, a human antiplatelet-derived growth factor receptor α monoclonal antibody that has antitumor activity in human sarcoma xenografts, combined with doxorubicin.
Researchers enrolled 15 patients with unresectable or metastatic soft-tissue sarcoma without prior anthracycline therapy in the phase 1b portion; 129 patients were enrolled in phase 2. Phase 2 patients were randomly assigned 1:1 to receive olaratumab 15 mg/kg IV on days 1 and 8 plus doxorubicin 75 mg/m2 on day 1 of each 21-day cycle, for a maximum of 8 cycles, or doxorubicin alone.
Results showed that median progression-free survival in the phase 2 part was 6.6 months (95% CI, 4.1-8.3) with olaratumab plus doxorubicin compared with 4.1 months (95% CI, 2.8-5.4) with doxorubicin (hazard ratio, 0.67; 95% CI, 0.44-1.02; P = .0615). Median overall survival was 26.5 months (95% CI, 20.9-31.7) and 14.7 months (95% CI, 9.2-17.1), respectively (hazard ratio, 0.46; 95% CI, 0.30-0.71; P = .0003).
The objective response rate for the combination was 18.2% (95% CI, 9.8—29.6) versus 11.9% (95% CI, 5.3-22.2) for doxorubicin alone.
Adverse events associated with olaratumab plus doxorubicin, versus those associated with doxorubicin alone, were neutropenia, mucositis, nausea, vomiting, and diarrhea. The rates of grade 3 or worse febrile neutropenia were similar in both treatment arms.
The findings suggest that olaratumab might provide a shift in the treatment of advanced soft-tissue sarcoma.
1. Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial [published online ahead of print June 9, 2016]. Lancet. doi: 10.1016/S0140-6736(16)30587-6.