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

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

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).

Original languageEnglish
Pages (from-to)3374-3381
Number of pages8
JournalJournal of Clinical Oncology
Volume32
Issue number30
DOIs
Publication statusPublished - 2014 Oct 20

Fingerprint

Ovarian Neoplasms
Disease-Free Survival
Platelet-Derived Growth Factor Receptors
Placebos
Drug Therapy
Therapeutics
Fallopian Tube Neoplasms
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor
Peritoneum
Survival Analysis
pazopanib
Neutropenia
Platinum
Gynecology
Thrombocytopenia
Obstetrics
Fatigue
Diarrhea

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Du Bois, A., Floquet, A., Kim, J. W., Rau, J., Del Campo, J. M., Friedlander, M., ... Harter, P. (2014). Incorporation of pazopanib in maintenance therapy of ovarian cancer. Journal of Clinical Oncology, 32(30), 3374-3381. https://doi.org/10.1200/JCO.2014.55.7348
Du Bois, Andreas ; Floquet, Anne ; Kim, Jae Weon ; Rau, Joern ; Del Campo, Josep M. ; Friedlander, Michael ; Pignata, Sandro ; Fujiwara, Keiichi ; Vergote, Ignace ; Colombo, Nicoletta ; Mirza, Mansoor R. ; Monk, Bradley J. ; Kimmig, Rainer ; Ray-Coquard, Isabelle ; Zang, Rongyu ; Diaz-Padilla, Ivan ; Baumann, Klaus H. ; Mouret-Reynier, Marie Ange ; Kim, Jae Hoon ; Kurzeder, Christian ; Lesoin, Anne ; Vasey, Paul ; Marth, Christian ; Canzler, Ulrich ; Scambia, Giovanni ; Shimada, Muneaki ; Calvert, Paula ; Pujade-Lauraine, Eric ; Kim, Byoung Gie ; Herzog, Thomas J. ; Mitrica, Ionel ; Schade-Brittinger, Carmen ; Wang, Qiong ; Crescenzo, Rocco ; Harter, Philipp. / Incorporation of pazopanib in maintenance therapy of ovarian cancer. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 30. pp. 3374-3381.
@article{f2aa4b2fc77b4fb788df60f66e127217,
title = "Incorporation of pazopanib in maintenance therapy of ovarian cancer",
abstract = "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).",
author = "{Du Bois}, Andreas and Anne Floquet and Kim, {Jae Weon} and Joern Rau and {Del Campo}, {Josep M.} and Michael Friedlander and Sandro Pignata and Keiichi Fujiwara and Ignace Vergote and Nicoletta Colombo and Mirza, {Mansoor R.} and Monk, {Bradley J.} and Rainer Kimmig and Isabelle Ray-Coquard and Rongyu Zang and Ivan Diaz-Padilla and Baumann, {Klaus H.} and Mouret-Reynier, {Marie Ange} and Kim, {Jae Hoon} and Christian Kurzeder and Anne Lesoin and Paul Vasey and Christian Marth and Ulrich Canzler and Giovanni Scambia and Muneaki Shimada and Paula Calvert and Eric Pujade-Lauraine and Kim, {Byoung Gie} and Herzog, {Thomas J.} and Ionel Mitrica and Carmen Schade-Brittinger and Qiong Wang and Rocco Crescenzo and Philipp Harter",
year = "2014",
month = "10",
day = "20",
doi = "10.1200/JCO.2014.55.7348",
language = "English",
volume = "32",
pages = "3374--3381",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "30",

}

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 2014, 'Incorporation of pazopanib in maintenance therapy of ovarian cancer', Journal of Clinical Oncology, vol. 32, no. 30, pp. 3374-3381. https://doi.org/10.1200/JCO.2014.55.7348

Incorporation of pazopanib in maintenance therapy of ovarian cancer. / Du Bois, Andreas; Floquet, Anne; Kim, Jae Weon; Rau, Joern; Del Campo, Josep M.; Friedlander, Michael; Pignata, Sandro; Fujiwara, Keiichi; Vergote, Ignace; Colombo, Nicoletta; Mirza, Mansoor R.; Monk, Bradley J.; Kimmig, Rainer; Ray-Coquard, Isabelle; Zang, Rongyu; Diaz-Padilla, Ivan; Baumann, Klaus H.; Mouret-Reynier, Marie Ange; Kim, Jae Hoon; Kurzeder, Christian; Lesoin, Anne; Vasey, Paul; Marth, Christian; Canzler, Ulrich; Scambia, Giovanni; Shimada, Muneaki; Calvert, Paula; Pujade-Lauraine, Eric; Kim, Byoung Gie; Herzog, Thomas J.; Mitrica, Ionel; Schade-Brittinger, Carmen; Wang, Qiong; Crescenzo, Rocco; Harter, Philipp.

In: Journal of Clinical Oncology, Vol. 32, No. 30, 20.10.2014, p. 3374-3381.

Research output: Contribution to journalArticle

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

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).

UR - http://www.scopus.com/inward/record.url?scp=84908334026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908334026&partnerID=8YFLogxK

U2 - 10.1200/JCO.2014.55.7348

DO - 10.1200/JCO.2014.55.7348

M3 - Article

C2 - 25225436

AN - SCOPUS:84908334026

VL - 32

SP - 3374

EP - 3381

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 30

ER -

Du Bois A, Floquet A, Kim JW, Rau J, Del Campo JM, Friedlander M et al. Incorporation of pazopanib in maintenance therapy of ovarian cancer. Journal of Clinical Oncology. 2014 Oct 20;32(30):3374-3381. https://doi.org/10.1200/JCO.2014.55.7348