ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer

Ursula A. Matulonis, Julie Lee, Brian Lasonde, William P. Tew, Afra Yehwalashet, Daniela Matei, Kian Behbakht, Jill Grothusen, Gini Fleming, Nita K. Lee, Jamie Arnott, Mark R. Bray, Graham Fletcher, Richard D. Brokx, Vincent Castonguay, Helen MacKay, Carolyn F. Sidor, Amit M. Oza

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Purpose: The purpose was to assess the activity and side effect profile of ENMD-2076, an oral anti-angiogenic and anti-proliferative kinase inhibitor, in platinum-resistant recurrent epithelial ovarian cancer (EOC), fallopian tube or peritoneal cancer. Archival tumour tissue was obtained for correlative analyses. Experimental design: This was an open-label single-arm Phase II study of single agent ENMD-2076 taken daily orally (PO). The primary objective was to determine the progression free survival (PFS) rate at 6 months of ENMD-2076 in platinum-resistant cancer based on RECIST v1.1. Secondary objectives included response rate (RR), duration of response, overall survival (OS) and safety. An exploratory analysis of archival tissue for mitotic index and angiogenesis was conducted in an attempt to identify a sensitive or resistant patient phenotype. Results: 64 patients were enrolled, and the PFS rate at 6 months was 22% with a median time to progression of 3.6 months. The median number of prior regimens was 2. The most common adverse events were fatigue, hypertension and diarrhoea with the most common Grade 3/4 events being hypertension and fatigue. None of the markers of mitotic index or angiogenesis evaluated in the archival tissue samples were predictive of greater benefit or resistance to ENMD-2076 treatment. Conclusions: ENMD-2076 has activity in platinum-resistant ovarian cancer, and observed toxicities were similar to other PO kinase inhibitors. Additional studies with ENMD-2076 are warranted, especially in combination with active chemotherapeutic agents in platinum-resistant patients. Further work to determine appropriate biomarkers for ENMD-2076 should be incorporated into new clinical studies.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalEuropean Journal of Cancer
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Angiogenesis Inhibitors
Platinum
Ovarian Neoplasms
Phosphotransferases
Mitotic Index
Disease-Free Survival
Fatigue
Fallopian Tube Neoplasms
Survival Rate
Hypertension
Neoplasms
ENMD 2076
Diarrhea
Research Design
Biomarkers
Phenotype
Safety
Survival

Keywords

  • ENMD-2076
  • Phase II
  • Recurrent ovarian cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer. / Matulonis, Ursula A.; Lee, Julie; Lasonde, Brian; Tew, William P.; Yehwalashet, Afra; Matei, Daniela; Behbakht, Kian; Grothusen, Jill; Fleming, Gini; Lee, Nita K.; Arnott, Jamie; Bray, Mark R.; Fletcher, Graham; Brokx, Richard D.; Castonguay, Vincent; MacKay, Helen; Sidor, Carolyn F.; Oza, Amit M.

In: European Journal of Cancer, Vol. 49, No. 1, 01.01.2013, p. 121-131.

Research output: Contribution to journalArticle

Matulonis, UA, Lee, J, Lasonde, B, Tew, WP, Yehwalashet, A, Matei, D, Behbakht, K, Grothusen, J, Fleming, G, Lee, NK, Arnott, J, Bray, MR, Fletcher, G, Brokx, RD, Castonguay, V, MacKay, H, Sidor, CF & Oza, AM 2013, 'ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer', European Journal of Cancer, vol. 49, no. 1, pp. 121-131. https://doi.org/10.1016/j.ejca.2012.07.020
Matulonis, Ursula A. ; Lee, Julie ; Lasonde, Brian ; Tew, William P. ; Yehwalashet, Afra ; Matei, Daniela ; Behbakht, Kian ; Grothusen, Jill ; Fleming, Gini ; Lee, Nita K. ; Arnott, Jamie ; Bray, Mark R. ; Fletcher, Graham ; Brokx, Richard D. ; Castonguay, Vincent ; MacKay, Helen ; Sidor, Carolyn F. ; Oza, Amit M. / ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer. In: European Journal of Cancer. 2013 ; Vol. 49, No. 1. pp. 121-131.
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abstract = "Purpose: The purpose was to assess the activity and side effect profile of ENMD-2076, an oral anti-angiogenic and anti-proliferative kinase inhibitor, in platinum-resistant recurrent epithelial ovarian cancer (EOC), fallopian tube or peritoneal cancer. Archival tumour tissue was obtained for correlative analyses. Experimental design: This was an open-label single-arm Phase II study of single agent ENMD-2076 taken daily orally (PO). The primary objective was to determine the progression free survival (PFS) rate at 6 months of ENMD-2076 in platinum-resistant cancer based on RECIST v1.1. Secondary objectives included response rate (RR), duration of response, overall survival (OS) and safety. An exploratory analysis of archival tissue for mitotic index and angiogenesis was conducted in an attempt to identify a sensitive or resistant patient phenotype. Results: 64 patients were enrolled, and the PFS rate at 6 months was 22{\%} with a median time to progression of 3.6 months. The median number of prior regimens was 2. The most common adverse events were fatigue, hypertension and diarrhoea with the most common Grade 3/4 events being hypertension and fatigue. None of the markers of mitotic index or angiogenesis evaluated in the archival tissue samples were predictive of greater benefit or resistance to ENMD-2076 treatment. Conclusions: ENMD-2076 has activity in platinum-resistant ovarian cancer, and observed toxicities were similar to other PO kinase inhibitors. Additional studies with ENMD-2076 are warranted, especially in combination with active chemotherapeutic agents in platinum-resistant patients. Further work to determine appropriate biomarkers for ENMD-2076 should be incorporated into new clinical studies.",
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T1 - ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer

AU - Matulonis, Ursula A.

AU - Lee, Julie

AU - Lasonde, Brian

AU - Tew, William P.

AU - Yehwalashet, Afra

AU - Matei, Daniela

AU - Behbakht, Kian

AU - Grothusen, Jill

AU - Fleming, Gini

AU - Lee, Nita K.

AU - Arnott, Jamie

AU - Bray, Mark R.

AU - Fletcher, Graham

AU - Brokx, Richard D.

AU - Castonguay, Vincent

AU - MacKay, Helen

AU - Sidor, Carolyn F.

AU - Oza, Amit M.

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N2 - Purpose: The purpose was to assess the activity and side effect profile of ENMD-2076, an oral anti-angiogenic and anti-proliferative kinase inhibitor, in platinum-resistant recurrent epithelial ovarian cancer (EOC), fallopian tube or peritoneal cancer. Archival tumour tissue was obtained for correlative analyses. Experimental design: This was an open-label single-arm Phase II study of single agent ENMD-2076 taken daily orally (PO). The primary objective was to determine the progression free survival (PFS) rate at 6 months of ENMD-2076 in platinum-resistant cancer based on RECIST v1.1. Secondary objectives included response rate (RR), duration of response, overall survival (OS) and safety. An exploratory analysis of archival tissue for mitotic index and angiogenesis was conducted in an attempt to identify a sensitive or resistant patient phenotype. Results: 64 patients were enrolled, and the PFS rate at 6 months was 22% with a median time to progression of 3.6 months. The median number of prior regimens was 2. The most common adverse events were fatigue, hypertension and diarrhoea with the most common Grade 3/4 events being hypertension and fatigue. None of the markers of mitotic index or angiogenesis evaluated in the archival tissue samples were predictive of greater benefit or resistance to ENMD-2076 treatment. Conclusions: ENMD-2076 has activity in platinum-resistant ovarian cancer, and observed toxicities were similar to other PO kinase inhibitors. Additional studies with ENMD-2076 are warranted, especially in combination with active chemotherapeutic agents in platinum-resistant patients. Further work to determine appropriate biomarkers for ENMD-2076 should be incorporated into new clinical studies.

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KW - Phase II

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