Incorporation of pazopanib in maintenance therapy of ovarian cancer

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 KurzederAnne 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

研究成果: Article査読

256 被引用数 (Scopus)

抄録

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).

本文言語English
ページ(範囲)3374-3381
ページ数8
ジャーナルJournal of Clinical Oncology
32
30
DOI
出版ステータスPublished - 2014 10月 20
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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