Abstract
BackgroundOlaratumab is a platelet-derived growth factor receptor-α (PDGFRα)-targeting monoclonal antibody blocking PDGFRα signaling. PDGFRα 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 (40 mg/m2, intravenous infusion) administered every 4 weeks with or without olaratumab (20 mg/kg, IV infusion) every 2 weeks. 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 4.2 months for olaratumab+liposomal doxorubicin and 4.0 months for liposomal doxorubicin (stratified hazard ratio [HR] = 1.043; 95% confidence interval [CI] 0.698–1.558; p = 0.837). Median OS was 16.6 months and 16.2 months 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 5.5 months (95% CI 1.6–9.2) and 3.7 months (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 grade ≥ 3 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.
Highlights
Olaratumab is a platelet-derived growth factor receptor-α (PDGFRα)-targeting monoclonal antibody blocking PDGFRα signaling
Subgroup analysis showed that patients with disease duration of less than 15.2 months had improvement in progression-free survival (PFS) with olaratumab+liposomal doxorubicin treatment (HR = 0.57; 95% confidence interval (CI) 0.29–1.12) (n = 50) compared with patients in the liposomal doxorubicin arm
Patients with a lower Cancer antigen 125 (CA125) (≤64.3) had higher PFS with olaratumab+liposomal doxorubicin treatment compared with patients in the liposomal doxorubicin arm, achieving an Hazard ratio (HR) of 0.5 (n = 27)
Summary
Olaratumab is a platelet-derived growth factor receptor-α (PDGFRα)-targeting monoclonal antibody blocking PDGFRα signaling. PDGFRα 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. Several phase II clinical studies of patients with platinum-resistant or -refractory disease have demonstrated the benefit of using doxorubicin in combination therapy with other agents [6,7,8,9,10,11,12]. Treatment guidelines recognize that combining traditional chemotherapeutic agents with drugs targeting growth factors/receptors may be more effective for treating platinum-resistant/−refractory recurrent ovarian cancer than chemotherapy alone [3, 4]
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