Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: A Gynecologic Oncology Group trial

Daniela Matei, Michael W. Sill, Heather A. Lankes, Koen DeGeest, Robert E. Bristow, David Mutch, S. Diane Yamada, David Cohn, Valerie Calvert, John Farley, Emanuel F. Petricoin, Michael J. Birrer

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Abstract

Purpose: Sorafenib is a kinase inhibitor targeting Raf and other kinases (ie, vascular endothelial growth factor receptor [VEGFR], platelet-derived growth factor receptor [PDGFR], Flt3, and c-KIT). This study assessed its activity and tolerability in patients with recurrent ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). Methods: This open-label, multi-institutional, phase II study used a two-stage design. Eligible patients had persistent or recurrent OC/PPC after one to two prior cytotoxic regimens, and they experienced progression within 12 months of platinum-based therapy. Treatment consisted of sorafenib 400 mg orally twice per day. Primary end points were progression-free survival (PFS) at 6 months and toxicity by National Cancer Institute criteria. Secondary end points were tumor response and duration of PFS and overall survival. Biomarker analyses included measurement of ERK and b-Raf expression in tumors and phosphorylation of ERK (pERK) in peripheral-blood lymphocytes (PBLs) before and after 1 month of treatment. Results: Seventy-three patients were enrolled, of which 71 were eligible. Fifty-nine eligible patients (83%) had measurable disease, and 12 (17%) had detectable disease. Significant grade 3 or 4 toxicities included the following: rash (n = 7), hand-foot syndrome (n = 9), metabolic (n = 10), GI (n = 3), cardiovascular (n = 2), and pulmonary (n = 2). Only patients with measurable disease were used to assess efficacy. Fourteen survived progression free for at least 6 months (24%; 90% CI, 15% to 35%). Two patients had partial responses (3.4%; 90% CI, 1% to 10%); 20 had stable disease; 30 had progressive disease; and seven could not have their tumor assessed. ERK and b-Raf were expressed in all tumors. Exploratory analyses indicated that pERK in post-treatment PBL specimens was associated with PFS. Conclusion: Sorafenib has modest antitumor activity in patients with recurrent OC, but the activity was at the expense of substantial toxicity.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

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Ovarian Neoplasms
Carcinoma
Disease-Free Survival
Neoplasms
raf Kinases
Phosphorylation
Hand-Foot Syndrome
Lymphocytes
Platelet-Derived Growth Factor Receptors
Vascular Endothelial Growth Factor Receptor
National Cancer Institute (U.S.)
Therapeutics
sorafenib
Exanthema
Platinum
Phosphotransferases
Biomarkers
Lung
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis : A Gynecologic Oncology Group trial. / Matei, Daniela; Sill, Michael W.; Lankes, Heather A.; DeGeest, Koen; Bristow, Robert E.; Mutch, David; Yamada, S. Diane; Cohn, David; Calvert, Valerie; Farley, John; Petricoin, Emanuel F.; Birrer, Michael J.

In: Journal of Clinical Oncology, Vol. 29, No. 1, 01.01.2011, p. 69-75.

Research output: Contribution to journalArticle

Matei, D, Sill, MW, Lankes, HA, DeGeest, K, Bristow, RE, Mutch, D, Yamada, SD, Cohn, D, Calvert, V, Farley, J, Petricoin, EF & Birrer, MJ 2011, 'Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: A Gynecologic Oncology Group trial', Journal of Clinical Oncology, vol. 29, no. 1, pp. 69-75. https://doi.org/10.1200/JCO.2009.26.7856
Matei, Daniela ; Sill, Michael W. ; Lankes, Heather A. ; DeGeest, Koen ; Bristow, Robert E. ; Mutch, David ; Yamada, S. Diane ; Cohn, David ; Calvert, Valerie ; Farley, John ; Petricoin, Emanuel F. ; Birrer, Michael J. / Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis : A Gynecologic Oncology Group trial. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 1. pp. 69-75.
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T1 - Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis

T2 - A Gynecologic Oncology Group trial

AU - Matei, Daniela

AU - Sill, Michael W.

AU - Lankes, Heather A.

AU - DeGeest, Koen

AU - Bristow, Robert E.

AU - Mutch, David

AU - Yamada, S. Diane

AU - Cohn, David

AU - Calvert, Valerie

AU - Farley, John

AU - Petricoin, Emanuel F.

AU - Birrer, Michael J.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Purpose: Sorafenib is a kinase inhibitor targeting Raf and other kinases (ie, vascular endothelial growth factor receptor [VEGFR], platelet-derived growth factor receptor [PDGFR], Flt3, and c-KIT). This study assessed its activity and tolerability in patients with recurrent ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). Methods: This open-label, multi-institutional, phase II study used a two-stage design. Eligible patients had persistent or recurrent OC/PPC after one to two prior cytotoxic regimens, and they experienced progression within 12 months of platinum-based therapy. Treatment consisted of sorafenib 400 mg orally twice per day. Primary end points were progression-free survival (PFS) at 6 months and toxicity by National Cancer Institute criteria. Secondary end points were tumor response and duration of PFS and overall survival. Biomarker analyses included measurement of ERK and b-Raf expression in tumors and phosphorylation of ERK (pERK) in peripheral-blood lymphocytes (PBLs) before and after 1 month of treatment. Results: Seventy-three patients were enrolled, of which 71 were eligible. Fifty-nine eligible patients (83%) had measurable disease, and 12 (17%) had detectable disease. Significant grade 3 or 4 toxicities included the following: rash (n = 7), hand-foot syndrome (n = 9), metabolic (n = 10), GI (n = 3), cardiovascular (n = 2), and pulmonary (n = 2). Only patients with measurable disease were used to assess efficacy. Fourteen survived progression free for at least 6 months (24%; 90% CI, 15% to 35%). Two patients had partial responses (3.4%; 90% CI, 1% to 10%); 20 had stable disease; 30 had progressive disease; and seven could not have their tumor assessed. ERK and b-Raf were expressed in all tumors. Exploratory analyses indicated that pERK in post-treatment PBL specimens was associated with PFS. Conclusion: Sorafenib has modest antitumor activity in patients with recurrent OC, but the activity was at the expense of substantial toxicity.

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