Comparison of Bevacizumab Alone or with Chemotherapy in Recurrent Ovarian Cancer Patients Katherine C. Fuh, Angeles A. Secord, Kerri S. Bevis, Warner Huh, Adam ElNaggar, Kevin Blansit, Rebecca Previs, Todd Tillmanns, Daniel S. Kapp, John K. Chan PII: DOI: Reference:
S0090-8258(15)30062-7 doi: 10.1016/j.ygyno.2015.06.041 YGYNO 975975
To appear in:
Gynecologic Oncology
Received date: Revised date: Accepted date:
29 April 2015 27 June 2015 30 June 2015
Please cite this article as: Katherine C. Fuh, Angeles A. Secord, Kerri S. Bevis, Warner Huh, Adam ElNaggar, Kevin Blansit, Rebecca Previs, Todd Tillmanns, Daniel S. Kapp, John K. Chan, Comparison of Bevacizumab Alone or with Chemotherapy in Recurrent Ovarian Cancer Patients, Gynecologic Oncology (2015), doi: 10.1016/j.ygyno.2015.06.041
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Comparison of Bevacizumab Alone or with Chemotherapy in Recurrent Ovarian Cancer Patients
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Katherine C. Fuh, M.D.,Ph.D.1,6,8, Angeles A. Secord, M.D.2, Kerri S. Bevis, M.D.3, Warner Huh, M.D.3, Adam ElNaggar, M.D.4, Kevin Blansit1,5, Rebecca Previs, M.D.2, Todd Tillmanns, M.D.4, Daniel S. Kapp M.D., Ph.D.7, John K. Chan, M.D.1,5 1
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Division of Gynecologic Oncology Helen Diller Family Comprehensive Cancer Center University Of California, San Francisco 1600 Divisadero Street San Francisco, CA 94143-1702 2
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Division of Gynecologic Oncology Department Of Obstetrics and Gynecology Duke University, School Of Medicine DUMC 3079 Durham, NC 27710 3
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Division of Gynecologic Oncology Department of Obstetrics and Gynecology University of Alabama at Birmingham 1700 6th Ave South Birmingham, AL 35233
5
4
The West Clinic . University of Tennessee 100 N. Humphreys Blvd, Memphis, TN 38120
Palo Alto Medical Foundation Research Institute 795 El Camino Real, Ames Building Palo Alto, CA 94301 6
Division of Gynecologic Oncology Department of Obstetrics and Gynecology Washington University, School of Medicine St. Louis, MO 63108 7
Department of Radiation Oncology Division of Gynecologic Oncology Department of Obstetrics and Gynecology Stanford University, School of Medicine 400 Pasteur Drive Stanford, CA 94305 8
1
ACCEPTED MANUSCRIPT
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Number of Pages: 18 Number of Tables: 4 Number of Figures: 1 Disclosure Statement: The authors report no financial disclosures. Financial Support: The authors would like to acknowledge The Dr. John A Kerner Research Fund for support of this project.
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Please address correspondence to: Dr. John K. Chan Division of Gynecologic Oncology California Pacific & Palo Alto Medical Foundation / Research Institute Sutter Cancer Research Consortium 3838 California Street San Francisco, CA 94115 Office: (415) 751-1847 Fax: (415) 387-2613 Email: [email protected]
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Portions of this study were presented as a poster at the 43rd Annual Society of Gynecologic Oncology 2012 in Austin, TX.
2
ACCEPTED MANUSCRIPT Abstract Background: To compare the efficacy of chemotherapy (C) combined with
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bevacizumab (Bev) versus Bev alone in recurrent, heavily pretreated epithelial ovarian
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cancer (EOC).
Methods: A multicenter analysis of patients treated from 2004 to 2011 was performed.
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Demographic, treatment, response, and adverse event information were obtained.
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Progression-free (PFS) and overall survival (OS) were analyzed. Results: Of 277 patients (median age: 58 years), the majority had Stage III and IV
MA
(86%) disease, and 72% had serous histology. 244 (88%) were treated with C+Bev and 33 (12%) with Bev. Corresponding median progression-free survival (PFS) was 8.7 and
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D
6.7 months, and median overall survival (OS) was 14.3 and 10.5 months, respectively. The chemotherapeutic agents combined with Bev and the median OS include:
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pegylated liposomal doxorubicin (n=19, OS of 20.4 months), taxanes (n=55, OS of 20.2 months), gemcitabine (n=106, OS of 14.1 months), topotecan (n=43, OS of 13 months), and cyclophosphamide (n=21, OS of 13 months). There was no significant difference in toxicities between the C+Bev vs. Bev alone group. Conclusion: This retrospective analysis supports that combination chemotherapy and bevacizumab prolongs PFS and OS compared with bevacizumab alone. Keywords: recurrent epithelial ovarian cancer; bevacizumab; chemotherapy; survival; platinum-resistant; liposomal doxorubicin, taxanes
3
ACCEPTED MANUSCRIPT Background Epithelial ovarian cancer (EOC) is the most lethal pelvic gynecologic
PT
malignancy[1]. In patients with recurrent, platinum-resistant, heavily pretreated disease,
RI
single agent chemotherapy has been generally recommended given the increased toxicity and lack of data showing additional benefit with combination chemotherapy [2-
SC
7].
(Bev) improved the
NU
In clinical trials, chemotherapy with bevacizumab
progression-free survival of those with primary and recurrent, platinum-sensitive and
MA
resistant disease compared to chemotherapy alone [8-14]. Preclinical studies have shown that Bev can potentially enhance the delivery of chemotherapeutic agents by
D
normalizing blood vessels and reducing interstitial fluid pressure [15-17]. More recently,
TE
a randomized clinical trial compared the efficacy of physician-selected chemotherapy
AC CE P
versus chemotherapy combined with bevacizumab in platinum-resistant ovarian cancer. These investigators found that the combination therapy including Bev improved the progression-free survival over chemotherapy alone (6.7 vs 3.4 months, p
S0090-8258(15)30062-7 doi: 10.1016/j.ygyno.2015.06.041 YGYNO 975975
To appear in:
Gynecologic Oncology
Received date: Revised date: Accepted date:
29 April 2015 27 June 2015 30 June 2015
Please cite this article as: Katherine C. Fuh, Angeles A. Secord, Kerri S. Bevis, Warner Huh, Adam ElNaggar, Kevin Blansit, Rebecca Previs, Todd Tillmanns, Daniel S. Kapp, John K. Chan, Comparison of Bevacizumab Alone or with Chemotherapy in Recurrent Ovarian Cancer Patients, Gynecologic Oncology (2015), doi: 10.1016/j.ygyno.2015.06.041
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Comparison of Bevacizumab Alone or with Chemotherapy in Recurrent Ovarian Cancer Patients
PT
Katherine C. Fuh, M.D.,Ph.D.1,6,8, Angeles A. Secord, M.D.2, Kerri S. Bevis, M.D.3, Warner Huh, M.D.3, Adam ElNaggar, M.D.4, Kevin Blansit1,5, Rebecca Previs, M.D.2, Todd Tillmanns, M.D.4, Daniel S. Kapp M.D., Ph.D.7, John K. Chan, M.D.1,5 1
SC
RI
Division of Gynecologic Oncology Helen Diller Family Comprehensive Cancer Center University Of California, San Francisco 1600 Divisadero Street San Francisco, CA 94143-1702 2
MA
NU
Division of Gynecologic Oncology Department Of Obstetrics and Gynecology Duke University, School Of Medicine DUMC 3079 Durham, NC 27710 3
AC CE P
TE
D
Division of Gynecologic Oncology Department of Obstetrics and Gynecology University of Alabama at Birmingham 1700 6th Ave South Birmingham, AL 35233
5
4
The West Clinic . University of Tennessee 100 N. Humphreys Blvd, Memphis, TN 38120
Palo Alto Medical Foundation Research Institute 795 El Camino Real, Ames Building Palo Alto, CA 94301 6
Division of Gynecologic Oncology Department of Obstetrics and Gynecology Washington University, School of Medicine St. Louis, MO 63108 7
Department of Radiation Oncology Division of Gynecologic Oncology Department of Obstetrics and Gynecology Stanford University, School of Medicine 400 Pasteur Drive Stanford, CA 94305 8
1
ACCEPTED MANUSCRIPT
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Number of Pages: 18 Number of Tables: 4 Number of Figures: 1 Disclosure Statement: The authors report no financial disclosures. Financial Support: The authors would like to acknowledge The Dr. John A Kerner Research Fund for support of this project.
MA
NU
SC
Please address correspondence to: Dr. John K. Chan Division of Gynecologic Oncology California Pacific & Palo Alto Medical Foundation / Research Institute Sutter Cancer Research Consortium 3838 California Street San Francisco, CA 94115 Office: (415) 751-1847 Fax: (415) 387-2613 Email: [email protected]
AC CE P
TE
D
Portions of this study were presented as a poster at the 43rd Annual Society of Gynecologic Oncology 2012 in Austin, TX.
2
ACCEPTED MANUSCRIPT Abstract Background: To compare the efficacy of chemotherapy (C) combined with
PT
bevacizumab (Bev) versus Bev alone in recurrent, heavily pretreated epithelial ovarian
RI
cancer (EOC).
Methods: A multicenter analysis of patients treated from 2004 to 2011 was performed.
SC
Demographic, treatment, response, and adverse event information were obtained.
NU
Progression-free (PFS) and overall survival (OS) were analyzed. Results: Of 277 patients (median age: 58 years), the majority had Stage III and IV
MA
(86%) disease, and 72% had serous histology. 244 (88%) were treated with C+Bev and 33 (12%) with Bev. Corresponding median progression-free survival (PFS) was 8.7 and
TE
D
6.7 months, and median overall survival (OS) was 14.3 and 10.5 months, respectively. The chemotherapeutic agents combined with Bev and the median OS include:
AC CE P
pegylated liposomal doxorubicin (n=19, OS of 20.4 months), taxanes (n=55, OS of 20.2 months), gemcitabine (n=106, OS of 14.1 months), topotecan (n=43, OS of 13 months), and cyclophosphamide (n=21, OS of 13 months). There was no significant difference in toxicities between the C+Bev vs. Bev alone group. Conclusion: This retrospective analysis supports that combination chemotherapy and bevacizumab prolongs PFS and OS compared with bevacizumab alone. Keywords: recurrent epithelial ovarian cancer; bevacizumab; chemotherapy; survival; platinum-resistant; liposomal doxorubicin, taxanes
3
ACCEPTED MANUSCRIPT Background Epithelial ovarian cancer (EOC) is the most lethal pelvic gynecologic
PT
malignancy[1]. In patients with recurrent, platinum-resistant, heavily pretreated disease,
RI
single agent chemotherapy has been generally recommended given the increased toxicity and lack of data showing additional benefit with combination chemotherapy [2-
SC
7].
(Bev) improved the
NU
In clinical trials, chemotherapy with bevacizumab
progression-free survival of those with primary and recurrent, platinum-sensitive and
MA
resistant disease compared to chemotherapy alone [8-14]. Preclinical studies have shown that Bev can potentially enhance the delivery of chemotherapeutic agents by
D
normalizing blood vessels and reducing interstitial fluid pressure [15-17]. More recently,
TE
a randomized clinical trial compared the efficacy of physician-selected chemotherapy
AC CE P
versus chemotherapy combined with bevacizumab in platinum-resistant ovarian cancer. These investigators found that the combination therapy including Bev improved the progression-free survival over chemotherapy alone (6.7 vs 3.4 months, p
