Medline ® Abstract for Reference 58
of 'First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and peritoneal cancer'
Incorporation of pazopanib in maintenance therapy of ovarian cancer.
du Bois A, Floquet A, Kim JW, Rau J, Del Campo JM, Friedlander M, Pignata S, Fujiwara K, Vergote I, Colombo N, Mirza MR, Monk BJ, Kimmig R, Ray-Coquard I, Zang R, Diaz-Padilla I, Baumann KH, Mouret-Reynier MA, Kim JH, Kurzeder C, Lesoin A, Vasey P, Marth C, Canzler U, Scambia G, Shimada M, Calvert P, Pujade-Lauraine E, Kim BG, Herzog TJ, Mitrica I, Schade-Brittinger C, Wang Q, Crescenzo R, Harter P
J Clin Oncol. 2014;32(30):3374.
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).
Andreas du Bois, Rainer Kimmig, Klaus H. Baumann, Christian Kurzeder, Ulrich Canzler, Philipp Harter, AGO Ovarian Cancer Study Group (AGO); Andreas du Bois, Christian Kurzeder, Philipp Harter, Kliniken Essen Mitte; Rainer Kimmig, West German Tumor Center, University of Duisburg-Essen, Essen; Joern Rau, Carmen Schade-Brittinger, Coordinating Center for Clinical Trials, Philipps-University of Marburg; Klaus H. Baumann, University of Marburg, Marburg; Ulrich Canzler, University Hospitals Carl Gustav Carus, Dresden, Germany; Anne Floquet, Isabelle Ray-Coquard, Marie-Ange Mouret-Reynier, Anne Lesoin, Eric Pujade-Lauraine, Groupe d'Investigateurs Nationaux pour l'Étude des Cancers Ovariens; Anne Floquet, Institut Bergonié, Bordeaux; Isabelle Ray-Coquard, Centre Léon Bérard, Lyon; Marie-Ange Mouret-Reynier, Centre Jean Perrin, Clermont-Ferrand; Anne Lesoin, Centre Oscar Lambret, Lille; Eric Pujade-Lauraine, Assistance Publique-Hôpitaux de Paris, UniversitéParis Descartes, Paris, France; Jae-Weon Kim, Jae-Hoon Kim, Korean Gynecologic Oncology Group; Jae-Weon Kim, Seoul National University; Jae-Hoon Kim, Yonsei University; Byoung-Gie Kim, Samsung Medical Center, Seoul, Republic of Korea; Josep M. del Campo, Ivan Diaz-Padilla, Spanish Ovarian Cancer Research Group; Josep M. del Campo, Vall d'Hebron University Hospital, Barcelona; Ivan Diaz-Padilla, Centro Integral Oncologico Clara Campal, HM Hospitales, Madrid, Spain; Michael Friedlander, Paul Vasey, Australian and New Zealand Gynecological Oncology Group; Michael Friedlander, The Prince of Wales Clinical School University of New South Wales, Randwick, New South Wales; Paul Vasey, Wesley Medical Centre, Auchenflower, Queensland, Australia; Sandro Pignata, Giovanni Scambia, Multicenter Italian Trials in Ovarian Cancer; Sandro Pignata, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Nicoletta Colombo, Mario Negri Gynecologic Oncology Group and University of Milan-Bicocca and European Institute of Oncology, Milan