TY - JOUR
T1 - Incorporation of pazopanib in maintenance therapy of ovarian cancer
AU - Du Bois, Andreas
AU - Floquet, Anne
AU - Kim, Jae Weon
AU - Rau, Joern
AU - Del Campo, Josep M.
AU - Friedlander, Michael
AU - Pignata, Sandro
AU - Fujiwara, Keiichi
AU - Vergote, Ignace
AU - Colombo, Nicoletta
AU - Mirza, Mansoor R.
AU - Monk, Bradley J.
AU - Kimmig, Rainer
AU - Ray-Coquard, Isabelle
AU - Zang, Rongyu
AU - Diaz-Padilla, Ivan
AU - Baumann, Klaus H.
AU - Mouret-Reynier, Marie Ange
AU - Kim, Jae Hoon
AU - Kurzeder, Christian
AU - Lesoin, Anne
AU - Vasey, Paul
AU - Marth, Christian
AU - Canzler, Ulrich
AU - Scambia, Giovanni
AU - Shimada, Muneaki
AU - Calvert, Paula
AU - Pujade-Lauraine, Eric
AU - Kim, Byoung Gie
AU - Herzog, Thomas J.
AU - Mitrica, Ionel
AU - Schade-Brittinger, Carmen
AU - Wang, Qiong
AU - Crescenzo, Rocco
AU - Harter, Philipp
N1 - Publisher Copyright:
© 2014, American Society for Microbiology. All Rights Reserved.
PY - 2014/10/20
Y1 - 2014/10/20
N2 - 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).
AB - 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).
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U2 - 10.1200/JCO.2014.55.7348
DO - 10.1200/JCO.2014.55.7348
M3 - Article
C2 - 25225436
AN - SCOPUS:84908334026
SN - 0732-183X
VL - 32
SP - 3374
EP - 3381
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 30
ER -
