Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16).

Gynecologic Cancer
Session Type and Session Title: 
Oral Abstract Session, Gynecologic Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr LBA5503)
Andreas Du Bois, Anne Floquet, Jae Weon Kim, Jörn Rau, Jose Maria Del Campo, Michael Friedlander, Sandro Pignata, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Mansoor Raza Mirza, Bradley J. Monk, Pauline Wimberger, Isabelle Ray-Coquard, Rongyu Zang, Ivan Diaz-Padilla, Klaus H. Baumann, Jae Hoon Kim, Philipp Harter, on behalf of an Intergroup consortium; Kliniken Essen Mitte, Essen, Germany; Institut Bergonié, Bordeaux, France; Seoul National University College of Medicine, Seoul, South Korea; Philipps University Marburg, Marburg, Germany; Vall d’Hebron Institute of Oncology, Barcelona, Spain; Prince of Wales Hospital, Sydney, Australia; National Cancer Institute of Naples, Naples, Italy; Saitama Medical University International Medical Center, Saitama, Japan; UZ Leuven, Leuven, Belgium; University of Milan-Bicocca, Milan, Italy; Department of Oncology; Rigshospitalet; Copenhagen University Hospital, Copenhagen, Denmark; Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, Phoenix, AZ; Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany; Centre Léon Bérard, Lyon, France; Shanghai Fudan University, Shanghai, China; Department of Medical Oncology, Centro Integral Oncologico “Clara Campal”, Madrid, Spain; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

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Abstract Disclosures


Background: Pazopanib is an oral, multikinase inhibitor of VEGFR-1, -2, -3, PDGFR-α and -β, and c-Kit. Preclinical and clinical studies support VEGF(R) and PDGF(R) as targets for AEOC treatment. This study evaluated the efficacy, safety, and tolerability of pazopanib maintenance therapy in patients who have not progressed after first-line chemotherapy for AEOC. Methods: Patients with histologically confirmed AEOC, FIGO II-IV, and no evidence of progression after surgery and ≥ 5 cycles of platinum-taxane chemotherapy were randomized 1:1 to receive 800 mg pazopanib once daily or placebo for up to 24 months. Primary endpoint was progression-free survival (PFS) by RECIST. Secondary endpoints included overall survival, PFS by GCIG criteria, safety, and quality of life. Results: Most of the 940 randomized patients had stage III/IV disease (91%) at initial diagnosis, and no residual disease after surgery (58%). The median time from diagnosis to randomization was 7.1 months in the placebo arm and 7.0 months in the pazopanib arm. The median follow-up was 24 months. Patients in the pazopanib arm had a prolonged PFS vs placebo (HR = 0.766; 95% CI: 0.64-0.91; p = 0.0021; medians 17.9 vs 12.3 months, respectively). Sensitivity and subgroup analyses of PFS, and analysis of PFS by GCIG criteria, were consistent with the primary analysis. The first interim analysis for OS (only 189 OS events = 20.1% of population) showed no difference between arms. Pazopanib mean exposure was shorter vs placebo (8.9 vs 11.7 months). Pazopanib treatment was associated with a higher incidence of adverse events (AEs) and serious AEs (26% vs 11%) vs placebo. The most common AEs were hypertension, diarrhea, nausea, headache, fatigue, and neutropenia. Fatal SAEs were reported in three patients on pazopanib and one patient on placebo. Conclusions: Pazopanib maintenance therapy provided a statistically significant and clinically meaningful PFS benefit in patients with AEOC; OS data are not mature. The safety profile of pazopanib in this setting was consistent with its established profile. Clinical trial information: NCT00866697.