Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer

I. Vergote; A. du Bois; A. Floquet; J. Rau; J. W. Kim; J. M. del Campo; M. Friedlander; S. Pignata; K. Fujiwara; N. Colombo; M. R. Mirza; B. J. Monk; I. Tsibulak; P. M. Calvert; T. J. Herzog; L. C. Hanker; J. Meunier; J. Y. Lee; A. Bologna; M. J. Carrasco-Alfonso; P. Harter

doi:10.1016/j.ygyno.2019.08.024

Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer

I. Vergote^*, A. du Bois, A. Floquet, J. Rau, J. W. Kim, J. M. del Campo, M. Friedlander, S. Pignata, K. Fujiwara, N. Colombo, M. R. Mirza, B. J. Monk, I. Tsibulak, P. M. Calvert, T. J. Herzog, L. C. Hanker, J. Meunier, J. Y. Lee, A. Bologna, M. J. Carrasco-AlfonsoP. Harter

^*Corresponding author for this work

Department of Gynecology and Obstetrics

66 Citations (Scopus)

Abstract

Objective: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). Methods: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II–IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. Results: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805–1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863–2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713–0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. Conclusion: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. Clinical trial information. ClinicalTrials.gov: NCT00866697.

Original language	English
Journal	Gynecologic Oncology
Volume	155
Issue number	2
Pages (from-to)	186-191
Number of pages	6
ISSN	0090-8258
DOIs	https://doi.org/10.1016/j.ygyno.2019.08.024
Publication status	Published - 11.2019

Funding

This study was initially sponsored by GlaxoSmithKline . Rights and responsibilities of the sponsor were transferred to Novartis as of May 1, 2015. Final analyses were performed by Novartis and confirmed by the AGO Study Group. The results are presented on behalf of all the participating sites of the AGO-OVAR16 study. We thank the patients for their participation in this study, as well as the staff at each study site, all of whom significantly contributed to the study. We thank Hong Zhang, an external contractor, for her support on final OS analyses and Anuradha Bandaru of Novartis Healthcare Pvt. Ltd. for providing medical editorial assistance for this manuscript. This study was initially sponsored by GlaxoSmithKline. Rights and responsibilities of the sponsor were transferred to Novartis as of May 1, 2015. Final analyses were performed by Novartis and confirmed by the AGO Study Group. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com, IV has no relationships to disclose. ADB received honoraria from PharmaMar, Tesaro; provided consulting or advisory board services to Advaxis, AstraZeneca, Genmab, Pfizer, Roche/Genentech. AF has provided consulting or advisory board services to AstraZeneca, Clovis, Roche, Tesaro; others for AstraZeneca, PharmaMar, Roche, Tesaro. JMC has provided consulting or advisory services to MSD; received travel accommodation or expenses from Merck-Serono. MF received honoraria from AstraZeneca, MSD; provided consulting or advisory board services to AstraZeneca, MSD; received research funding from BeiGene. SP has received honoraria from Roche, AstraZeneca, Claris, Tesaro, MSD, Pfizer; provided consulting or advisory board services to Claris, Tesaro, AstraZeneca; was part of speakers' bureau for AstraZeneca, Tesaro; received research funding from Roche, Tesaro, MSD. KF received honoraria from Bayer, Chugai Pharma, Daiichi Sankyo, Eisai, Janssen Oncology, Kyowa Hakko Kirin, Lilly Japan, Nippon Kayaku, Ono Pharmaceutical, Taiho Pharmaceutical, Zeria Pharmaceutical; provided consulting or advisory board services to AstraZeneca, Chugai Pharma, Eisai, MSD, Pfizer, Taiho Pharmaceutical, Takeda; received research funding from AstraZeneca, Chugai Pharma, Eisai, GlaxoSmithKline, Immunogen, Kaken Pharmaceutical, Lilly, MSD, Oncotherapeutics, Ono Pharmaceutical, Pfizer, Shionogi, Taiho Pharmaceutical, Zeria Pharmaceutical. NC is an employee of Ignyta; provided consulting or advisory board services to Amgen, AstraZeneca, Clovis Oncology, MSD Oncology, Pfizer, PharmaMar, Roche/Genentech. MRM is a part of the leadership in Karyopharm Therapeutics, SeraCare and has stock; other ownership interests with Karyopharm Therapeutics, SeraCare; received honoraria from Advaxis, AstraZeneca, Cerulean Pharma, Clovis Oncology, Novocure, Pfizer, Roche, Tesaro; provided consulting and advisory board services to AstraZeneca, Cerulean Pharma, Clovis Oncology, Genmab, Karyopharm Therapeutics, Novocure, Pfizer, Tesaro; received research funding from AstraZeneca, Boehringer Ingelheim, Pfizer, Tesaro; received travel accommodations and expenses from AstraZeneca, Karyopharm Therapeutics, Pfizer, Roche, SeraCare, Tesaro. BJM is a part of the leadership in US Oncology; received honoraria from AbbVie, Advaxis, Amgen, AstraZeneca, Bayer, Biodesix, Cerulean Pharma, Clovis Oncology, GlaxoSmithKline, Gradalis, Immunogen, Incyte, Insys Therapeutics, Janssen, Mateon Therapeutics, Merck, Myriad Pharmaceuticals, NuCana BioMed, OXiGENE, Perthera, Pfizer, Precision Oncology, Roche/Genentech, Tesaro, Verastem, Vermillion; provided consulting or advisory support to AbbVie, Advaxis, Amgen, AstraZeneca, Bayer, Biodesix, Cerulean Pharma, Clovis Oncology, GlaxoSmithKline, Gradalis, Immunogen, Incyte, Insys Therapeutics, Mateon Therapeutics, Merck, Myriad Pharmaceuticals, NuCana BioMed, OXiGENE, Perthera, Pfizer, Precision Oncology, Roche/Genentech, Tesaro, Verastem, Vermillion; was part of speakers' bureau for AstraZeneca, Clovis Oncology, Janssen, Roche/Genentech, Tesaro; received research funding from Advaxis, Amgen, Array BioPharma, AstraZeneca, Genentech, Immunogen, Janssen, Lilly, Morphotek, Novartis, NuCana, Pfizer, Regeneron, Tesaro. IT has received travel accommodation or expenses from Roche, AstraZeneca, Amgen. PMC has received travel accommodations or expenses from Pfizer, SERVIER. TJH has provided scientific advisory board services to AstraZeneca, Caris, Clovis, Genentech, J&J, Tesaro. LCH has received honoraria from AstraZeneca, Roche, Tesaro, PharmaMar; provided consulting and advisory board services to AstraZeneca, Roche, Tesaro, PharmaMar; received travel accommodation or expenses from AstraZeneca, Roche, Tesaro, PharmaMar. MJC-A is an employee of Novartis; has stock or other ownership interest with Novartis. PH has received honoraria from AstraZeneca, Roche, Tesaro, Stryker and EUI lab, MSD; provided consulting and advisory board services to AstraZeneca, Roche, Tesaro, Eli Lilly, Clovis, Immunogen; received research funding from AstraZeneca, Roche, Boehringer Ingelheim, Tesaro. JR, J-WK, JM, JYL, and AB have no relations to disclose. IV has no relationships to disclose. ADB received honoraria from PharmaMar, Tesaro; provided consulting or advisory board services to Advaxis, AstraZeneca, Genmab, Pfizer, Roche/Genentech. AF has provided consulting or advisory board services to AstraZeneca, Clovis, Roche, Tesaro; others for AstraZeneca, PharmaMar, Roche, Tesaro. JMC has provided consulting or advisory services to MSD; received travel accommodation or expenses from Merck-Serono. MF received honoraria from AstraZeneca, MSD; provided consulting or advisory board services to AstraZeneca, MSD; received research funding from BeiGene. SP has received honoraria from Roche, AstraZeneca, Claris, Tesaro, MSD, Pfizer; provided consulting or advisory board services to Claris, Tesaro, AstraZeneca; was part of speakers' bureau for AstraZeneca, Tesaro; received research funding from Roche, Tesaro, MSD. KF received honoraria from Bayer, Chugai Pharma, Daiichi Sankyo, Eisai, Janssen Oncology, Kyowa Hakko Kirin, Lilly Japan, Nippon Kayaku, Ono Pharmaceutical, Taiho Pharmaceutical, Zeria Pharmaceutical; provided consulting or advisory board services to AstraZeneca, Chugai Pharma, Eisai, MSD, Pfizer, Taiho Pharmaceutical, Takeda; received research funding from AstraZeneca, Chugai Pharma, Eisai, GlaxoSmithKline, Immunogen, Kaken Pharmaceutical, Lilly, MSD, Oncotherapeutics, Ono Pharmaceutical, Pfizer, Shionogi, Taiho Pharmaceutical, Zeria Pharmaceutical. NC is an employee of Ignyta; provided consulting or advisory board services to Amgen, AstraZeneca, Clovis Oncology, MSD Oncology, Pfizer, PharmaMar, Roche/Genentech. MRM is a part of the leadership in Karyopharm Therapeutics, SeraCare and has stock; other ownership interests with Karyopharm Therapeutics, SeraCare; received honoraria from Advaxis, AstraZeneca, Cerulean Pharma, Clovis Oncology, Novocure, Pfizer, Roche, Tesaro; provided consulting and advisory board services to AstraZeneca, Cerulean Pharma, Clovis Oncology, Genmab, Karyopharm Therapeutics, Novocure, Pfizer, Tesaro; received research funding from AstraZeneca, Boehringer Ingelheim, Pfizer, Tesaro; received travel accommodations and expenses from AstraZeneca, Karyopharm Therapeutics, Pfizer, Roche, SeraCare, Tesaro. BJM is a part of the leadership in US Oncology; received honoraria from AbbVie, Advaxis, Amgen, AstraZeneca, Bayer, Biodesix, Cerulean Pharma, Clovis Oncology, GlaxoSmithKline, Gradalis, Immunogen, Incyte, Insys Therapeutics, Janssen, Mateon Therapeutics, Merck, Myriad Pharmaceuticals, NuCana BioMed, OXiGENE, Perthera, Pfizer, Precision Oncology, Roche/Genentech, Tesaro, Verastem, Vermillion; provided consulting or advisory support to AbbVie, Advaxis, Amgen, AstraZeneca, Bayer, Biodesix, Cerulean Pharma, Clovis Oncology, GlaxoSmithKline, Gradalis, Immunogen, Incyte, Insys Therapeutics, Mateon Therapeutics, Merck, Myriad Pharmaceuticals, NuCana BioMed, OXiGENE, Perthera, Pfizer, Precision Oncology, Roche/Genentech, Tesaro, Verastem, Vermillion; was part of speakers' bureau for AstraZeneca, Clovis Oncology, Janssen, Roche/Genentech, Tesaro; received research funding from Advaxis, Amgen, Array BioPharma, AstraZeneca, Genentech, Immunogen, Janssen, Lilly, Morphotek, Novartis, NuCana, Pfizer, Regeneron, Tesaro. IT has received travel accommodation or expenses from Roche, AstraZeneca, Amgen. PMC has received travel accommodations or expenses from Pfizer, SERVIER. TJH has provided scientific advisory board services to AstraZeneca, Caris, Clovis, Genentech, J&J, Tesaro. LCH has received honoraria from AstraZeneca, Roche, Tesaro, PharmaMar; provided consulting and advisory board services to AstraZeneca, Roche, Tesaro, PharmaMar; received travel accommodation or expenses from AstraZeneca, Roche, Tesaro, PharmaMar. MJC-A is an employee of Novartis; has stock or other ownership interest with Novartis. PH has received honoraria from AstraZeneca, Roche, Tesaro, Stryker and EUI lab, MSD; provided consulting and advisory board services to AstraZeneca, Roche, Tesaro, Eli Lilly, Clovis, Immunogen; received research funding from AstraZeneca, Roche, Boehringer Ingelheim, Tesaro. JR, J-WK, JM, JYL, and AB have no relations to disclose.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Research Area: Luebeck Integrated Oncology Network (LION)
Centers: University Cancer Center Schleswig-Holstein (UCCSH)

Access to Document

10.1016/j.ygyno.2019.08.024

Cite this

Vergote, I., du Bois, A., Floquet, A., Rau, J., Kim, J. W., del Campo, J. M., Friedlander, M., Pignata, S., Fujiwara, K., Colombo, N., Mirza, M. R., Monk, B. J., Tsibulak, I., Calvert, P. M., Herzog, T. J., Hanker, L. C., Meunier, J., Lee, J. Y., Bologna, A., ... Harter, P. (2019). Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer. Gynecologic Oncology, 155(2), 186-191. https://doi.org/10.1016/j.ygyno.2019.08.024

@article{fb238a8514574b74be9a9f7a0030470f,

title = "Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer",

abstract = "Objective: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). Methods: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II–IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. Results: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7\% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95\% confidence interval [CI]: 0.805–1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95\% CI: 0.863–2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95\% CI: 0.713–0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. Conclusion: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. Clinical trial information. ClinicalTrials.gov: NCT00866697.",

author = "I. Vergote and \{du Bois\}, A. and A. Floquet and J. Rau and Kim, \{J. W.\} and \{del Campo\}, \{J. M.\} and M. Friedlander and S. Pignata and K. Fujiwara and N. Colombo and Mirza, \{M. R.\} and Monk, \{B. J.\} and I. Tsibulak and Calvert, \{P. M.\} and Herzog, \{T. J.\} and Hanker, \{L. C.\} and J. Meunier and Lee, \{J. Y.\} and A. Bologna and Carrasco-Alfonso, \{M. J.\} and P. Harter",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = nov,

doi = "10.1016/j.ygyno.2019.08.024",

language = "English",

volume = "155",

pages = "186--191",

journal = "Gynecologic Oncology",

issn = "0090-8258",

publisher = "Academic Press Inc.",

number = "2",

}

Vergote, I, du Bois, A, Floquet, A, Rau, J, Kim, JW, del Campo, JM, Friedlander, M, Pignata, S, Fujiwara, K, Colombo, N, Mirza, MR, Monk, BJ, Tsibulak, I, Calvert, PM, Herzog, TJ, Hanker, LC, Meunier, J, Lee, JY, Bologna, A, Carrasco-Alfonso, MJ & Harter, P 2019, 'Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer', Gynecologic Oncology, vol. 155, no. 2, pp. 186-191. https://doi.org/10.1016/j.ygyno.2019.08.024

Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer. / Vergote, I.; du Bois, A.; Floquet, A. et al.
In: Gynecologic Oncology, Vol. 155, No. 2, 11.2019, p. 186-191.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer

AU - Vergote, I.

AU - du Bois, A.

AU - Floquet, A.

AU - Rau, J.

AU - Kim, J. W.

AU - del Campo, J. M.

AU - Friedlander, M.

AU - Pignata, S.

AU - Fujiwara, K.

AU - Colombo, N.

AU - Mirza, M. R.

AU - Monk, B. J.

AU - Tsibulak, I.

AU - Calvert, P. M.

AU - Herzog, T. J.

AU - Hanker, L. C.

AU - Meunier, J.

AU - Lee, J. Y.

AU - Bologna, A.

AU - Carrasco-Alfonso, M. J.

AU - Harter, P.

PY - 2019/11

Y1 - 2019/11

N2 - Objective: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). Methods: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II–IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. Results: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805–1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863–2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713–0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. Conclusion: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. Clinical trial information. ClinicalTrials.gov: NCT00866697.

AB - Objective: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). Methods: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II–IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. Results: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805–1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863–2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713–0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. Conclusion: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. Clinical trial information. ClinicalTrials.gov: NCT00866697.

UR - https://www.scopus.com/pages/publications/85071963488

U2 - 10.1016/j.ygyno.2019.08.024

DO - 10.1016/j.ygyno.2019.08.024

M3 - Journal articles

C2 - 31519320

AN - SCOPUS:85071963488

SN - 0090-8258

VL - 155

SP - 186

EP - 191

JO - Gynecologic Oncology

JF - Gynecologic Oncology

IS - 2

ER -

Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer

Abstract

Funding

UN SDGs

Research Areas and Centers

Access to Document

Other files and links

Fingerprint

Cite this