Phase II Study Shows Addition of Pazopanib to Paclitaxel Improves Progression-Free Survival in Platinum-Resistant/Refractory Advanced Ovarian Cancer
In an Italian randomized phase II trial reported in The Lancet Oncology, Pignata et al found that the addition of the antiangiogenic multikinase inhibitor pazopanib (Votrient) to weekly paclitaxel significantly improved progression-free survival in patients with platinum-resistant/refractory advanced ovarian cancer.
Study Details
In the open-label study, 74 patients from Italian hospitals were randomly assigned between December 2010 and February 2013 to receive weekly paclitaxel 80 mg/m² with (n = 37) or without pazopanib 800 mg/d (n = 37). Patients had to have received a maximum of two prior lines of chemotherapy and had to have no residual peripheral neurotoxicity. The primary endpoint was progression-free survival.
The combination and paclitaxel groups were generally balanced for age (median 56 and 58 years), resistance (76% and 75%) and refractoriness (24% and 22%) to platinum therapy, prior lines of chemotherapy (one in 46% and 42%, two in 46% and 50%, three in 8% in both), and histology (eg, serous in 70% and 67%, endometrioid in 11% and 6%, clear cell in 3% and 8%).
Efficacy Outcome
Median follow-up was 16.1 months. Median progression-free survival was 6.35 months (95% confidence interval [CI] = 5.36–11.02 months) in the pazopanib-paclitaxel group vs 3.49 months (95% CI = 2.01–5.66 months) in the paclitaxel group (hazard ratio [HR] = 0.42, P = .0002).
Objective response rates were 56% vs 25% (P = .008), with complete response in 8% vs 3%. Median overall survival was 19.1 vs 13.7 months (HR = 0.60, P = .056).
Adverse Events
Any grade leukopenia, neutropenia, fatigue, epistaxis, hypertension, diarrhea, mucositis, increased alanine transaminase or aspartate transaminase, increased amylase, and sensory neuropathy were significantly more common (all P < .05) in the pazopanib-paclitaxel group. Grade 3 or 4 adverse events occurred in 59% vs 31% of patients, with the most common being neutropenia (30% vs 3%), fatigue (11% vs 6%), leukopenia (11% vs 3%), hypertension (8% vs 0%), increased alanine transaminase or aspartate transaminase (8% vs 0%), and anemia (5% vs 14%). A grade 3 thromboembolic event occurred in one patient (3%) in each group. Ileal perforation occurred in one patient in the combination group. Adverse events led to discontinuation of treatment in 8% vs 11%.
The investigators concluded: “Our findings suggest that a phase III study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted.”
Sandro Pignata, MD, of Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione GPascale” IRCCS, Naples, Italy, is the corresponding author of The Lancet Oncology article.
The study was funded by the National Cancer Institute of Napoli and GlaxoSmithKline. Dr. Pignata and Francesco Raspagliesi, MD, have received research funding from GlaxoSmithKline.
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