Pazopanib based oral metronomic therapy for platinum resistant/refractory epithelial ovarian cancer: A phase II, open label, randomized, controlled trial.

BACKGROUND: Treatment of patients with platinum resistant/refractory epithelial ovarian cancer (EOC) is an unmet need. We evaluated the role of oral metronomic therapy in this setting.

PATIENTS AND METHODS: Between October 2017 and September 2019 seventy five patients with platinum resistant/refractory EOC were enrolled. Patients received oral etoposide (50 mg, day 1 to 14, cyclophosphamide 50 mg, day 1 to 28, every 4 weeks (Arm A, n = 38). Patients in Arm- B (n = 37) received Pazopanib (400 mg once daily) in addition to etoposide and cyclophosphamide. Quality of life (QoL) was evaluated using the EORTC questionnaire. Serum VEGF and PDGF were estimated at baseline, after 3rd and 6th cycle. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and QoL.

RESULTS: Patients characteristics were well matched. Median PFS was higher in arm B, 5.1 months (95% CI 3.13 to10.33) compared to 3.4 months (95% CI 3.0 to 6.53) in arm A, p = 0.045. Median OS has 'not reached' in Arm B compared to 11.2 months (95% CI, 5.66 - not reached) in arm A, p = 0.032. Therapy was tolerated well; oral mucositis (p = 0.36) and fatigue (p = 0.08) being more in arm B. QoL assessment revealed modest improvement in 'symptom scales' in Arm B. Serum VEGF and PDGF levels decreased with therapy in both arms (Arm A-p < 0.0001, Arm B-p < 0.016).

CONCLUSION: Addition of pazopanib to etoposide and cyclophosphamide could be a novel oral combination for metronomic therapy for platinum resistant/refractory EOC.

TRIAL REGISTRATION: CTRI/2017/10/010219.