Incorporation of pazopanib in maintenance therapy of ovarian cancer.

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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%).

CONCLUSION:

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).

• Authors: Andreas du Bois, Anne Floquet, Jae-Weon Kim, Joern Rau, Josep M del Campo, Michael Friedlander, Sandro Pignata, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Mansoor R Mirza, Bradley J Monk, Rainer Kimmig, Isabelle Ray-Coquard, Rongyu Zang, Ivan Diaz-Padilla, Klaus H Baumann, Marie-Ange Mouret-Reynier, Jae-Hoon Kim, Christian Kurzeder, Anne Lesoin, Paul Vasey, Christian Marth, Ulrich Canzler, Giovanni Scambia, Muneaki Shimada, Paula Calvert, Eric Pujade-Lauraine, Byoung-Gie Kim, Thomas J Herzog, Ionel Mitrica, Carmen Schade-Brittinger, Qiong Wang, Rocco Crescenzo, Philipp Harter
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 30 Pg. 3374-82 (Oct 20 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 25225436 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Angiogenesis Inhibitors
• Indazoles
• Pyrimidines
• Sulfonamides
• pazopanib
• Receptors, Vascular Endothelial Growth Factor

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Disease-Free Survival
• Double-Blind Method
• Female
• Humans
• Indazoles
• Ovarian Neoplasms (drug therapy, mortality)
• Pyrimidines (adverse effects, therapeutic use)
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors)
• Sulfonamides (adverse effects, therapeutic use)