Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

TLDR

Pazopanib is an oral multikinase inhibitor targeting VEGFR, PDGFR, and c‑Kit, and preclinical and clinical evidence supports these pathways as therapeutic targets in advanced ovarian cancer. The study aimed to evaluate the efficacy of pazopanib maintenance therapy in advanced ovarian cancer patients who had not progressed after first‑line chemotherapy and to identify subgroups where benefit may outweigh toxicity. A randomized, double‑blind, placebo‑controlled trial enrolled 940 FIGO stage II–IV patients who received either 800 mg daily pazopanib or placebo for up to 24 months, with progression‑free survival by RECIST 1.0 as the primary endpoint. Pazopanib maintenance prolonged median progression‑free survival by 5.6 months (HR 0.77, 95 % CI 0.64–0.91) but raised grade 3/4 adverse events and discontinuation rates, and did not improve overall survival.

Abstract

Pazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.Nine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.Maintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).Pazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).