Maintenance Pazopanib in Ovarian Cancer: No Survival Benefit, High Rate of Complications

(Sept. 25, 2014) Maintenance therapy with the oral agent pazopanib improved progression free survival (PFS) by a median of 5.6 months in patients with advanced ovarian cancer but did not impact overall survival, according to the results of a phase III randomized trial reported in the Journal of Clinical Oncology.

In this clinical trial, which was sponsored by pazonanib manufacturer GlaxsoSmithKline, a total of 940 patients with ovarian, fallopian tube, or peritoneum cancers were randomized to receive either pazopanib once daily, or placebo for up to 24 months. Patients had stage II through IV disease and had to have not progressed after first-line platinum-based chemotherapy.

After a median of 24.3 months of follow-up, the median progression free survival was 17.9 months in the pazopanib arm and 12.3 months in the placebo arm. However, an interim survival analysis did not show any significant difference between the two study arms after events in 36.5% of the study population. In addition, patients in the pazonpanib arm were more likely to discontinue treatment, and reported more serious complications.

Lead author Andreas du Bois, MD, PhD, a clinician and researcher in the department of Gynecology and Gynecologic Oncology, Essen, Germany, and colleagues concluded that additional analyses are needed to identify subgroups of patients for whom the improved efficacy balances out the increased toxicity of the maintenance therapy.

In an editorial accompanying the study, Kate E. Oliver, MD, of Walter Reed National Military Medical Center in Bethesda, Maryland, and William P. McGuire, MD, of Inova Fairfax Hospital, Annandale in Virginia, highlighted the relatively high discontinuation rate of patients in the pazopanib arm and its unfavorable benefit-to-risk profile. Noting that owing to previous study results, GSK had withdrawn its application in the European Union for approval of pazopanib as a maintenance therapy for ovarian cancer, they wrote, “Despite the positive PFS results reported by this [trial] and other phase III trials in [ovarian cancer], development of pazopanib in the maintenance setting will undoubtedly falter.”

In their editorial, they warned that the increased toxicity observed with pazopanib and other anti-angiogenic agents as well as the possibility that these treatments may not benefit a subset of patients “should raise caution regarding the [indiscriminate] use of surrogate end points such as PFS for drug approval.”

Adapted from (free registration required).


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