Andreas du Bois1, Anne Floquet1, Jae‐Weon Kim1,2, Jörn Rau1, Josep M. del Campo1, Michael Friedlander1, Sandro Pignata1, Keiichi Fujiwara1,3, Ignace Vergote4,1, Nicoletta Colombo1, Mansoor Raza Mirza1, Bradley J. Monk1, Rainer Kimmig1, Isabelle Ray‐Coquard1, Rongyu Zang1, Iván Díaz-Padilla1, Klaus Baumann1, Marie‐Ange Mouret‐Reynier1, Jae‐Hoon Kim1,5, Christian Kurzeder1,6, Anne Lesoin1, P. Vasey1, Christian Marth1, Ulrich Canzler1,7, Giovanni Scambia1, Muneaki Shimada1,3, Paula Calvert1, Éric Pujade-Lauraine1, Byoung‐Gie Kim1, Thomas J. Herzog1, Ionel Mitrica1,8, Carmen Schade‐Brittinger1, Qiong Wang1,8, Rocco J. Crescenzo1,8, Philipp Harter1
1Andreas 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,...
2Seoul National University
3Japanese Gynecologic Oncology Group
4KU, Leuven
5, Yonsei University
6Innsbruck Medical University
7University of Marburg
8(GlaxoSmithKline)
Tóm tắt
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).
