Randomized phase II study of the PDGFR antibody olaratumab plus liposomal doxorubicin versus liposomal doxorubicin alone in patients with platinum-refractory or platinum-resistant advanced ovarian cancer

BackgroundOlaratumab is a platelet-derived growth factor receptor- (PDGFR)-targeting monoclonal antibody blocking PDGFR signaling. PDGFR expression is associated with a more aggressive phenotype and poor ovarian cancer outcomes. This randomized, open label phase II study evaluated olaratumab plus liposomal doxorubicin compared with liposomal doxorubicin alone in advanced ovarian cancer patients.MethodsPatients with platinum-refractory or platinum-resistant advanced ovarian cancer were randomized 1:1 to receive liposomal doxorubicin (40mg/m(2), intravenous infusion) administered every 4weeks with or without olaratumab (20mg/kg, IV infusion) every 2weeks. Patients were stratified based on prior response to platinum therapy (refractory vs resistant). The primary efficacy endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, duration of response, and safety.ResultsA total of 123 patients were treated (62 olaratumab+liposomal doxorubicin; 61 liposomal doxorubicin). Median PFS was 4.2months for olaratumab+liposomal doxorubicin and 4.0months for liposomal doxorubicin (stratified hazard ratio [HR]=1.043; 95% confidence interval [CI] 0.698-1.558; p=0.837). Median OS was 16.6months and 16.2months in the olaratumab+liposomal doxorubicin and liposomal doxorubicin arms, respectively (HR=1.098; 95% CI 0.71-1.71). In the platinum-refractory subgroup, median PFS was 5.5months (95% CI 1.6-9.2) and 3.7months (95% CI 1.9-9.2) in the olaratumab+liposomal doxorubicin (n=15) and liposomal doxorubicin arms (n=16), respectively (HR=0.85; 95% CI 0.38-1.91). Overall, 59.7% (olaratumab+liposomal doxorubicin) and 65.6% (liposomal doxorubicin) of patients reported grade3 adverse events regardless of causality. The most common treatment-emergent adverse events (all grades) regardless of causality were fatigue related (61%), nausea (57%), and constipation (52%) with olaratumab+liposomal doxorubicin and nausea (64%), fatigue related (62%), and mucositis (46%) with liposomal doxorubicin.ConclusionsThe addition of olaratumab to liposomal doxorubicin did not result in significant prolongation of PFS or OS in platinum-resistant or platinum-refractory ovarian cancer.Trial registrationClinicalTrials.gov identifier: NCT00913835; registered June 2, 2009.