OBJECTIVES: Soft tissue sarcomas (STSs) are cancers originating in connective tissue; in 50% of cases, patients initially present with or develop advanced or metastatic disease. Prognosis is poor with standard-of-care, anthracycline-containing systemic therapy; median overall survival (OS) is approximately 1 year. A recent phase 2 trial investigated olaratumab, a human anti-platelet-derived growth factor receptor alpha monoclonal antibody, in combination with doxorubicin, for treatment of advanced STS (aSTS). Our objective was to assess the clinical efficacy and safety of olaratumab compared with current standard-of-care therapies in aSTS.
METHODS: We conducted a systematic literature review of phase 2 and 3 aSTS trials. Network meta-analyses (NMAs) were conducted for endpoints including OS, progression-free survival (PFS), and discontinuation due to adverse events (AEs). For survival outcomes, NMAs were performed on hazard ratios (HRs) and also using fractional polynomial models (FPMs).
RESULTS: A total of 54 comparative studies were identified, of which six studied olaratumab or current standard-ofcare therapies and could be linked in a network. The NMAs analyzed the seven regimens within the network: one regimen each for doxorubicin monotherapy (Dox), olaratumab in combination with doxorubicin (OlaDox), and gemcitabine in combination with docetaxel (GemDoc); and four different dose regimens of ifosfamide in combination with doxorubicin (IfoDox). The OlaDox regimen demonstrated improved OS compared with all included regimens; the improvement was statistically significant (P-values < 0.023 for the HR-based NMA) for all regimens except one IfoDox regimen. OlaDox also showed improved PFS compared with all included regimens; based on FPMs the improvement was statistically significant for Dox, one IfoDox regimen, and GemDoc. For safety, OlaDox showed a significantly lower rate of discontinuation due to AEs compared with all regimens except Dox and one IfoDox regimen.
CONCLUSIONS: OlaDox demonstrated more favorable results than comparators in terms of aSTS survival endpoints and discontinuation due to AEs.
