PRECEDENT: A randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer

R. Wendel Naumann, Robert L. Coleman, Robert A. Burger, Edward A. Sausville, Elzbieta Kutarska, Sharad A Ghamande, Nashat Y. Gabrail, Stephen E. DePasquale, Elzbieta Nowara, Lucy Gilbert, Robert H. Gersh, Michael G. Teneriello, Wael A. Harb, Panagiotis A. Konstantinopoulos, Richard T. Penson, James T. Symanowski, Chandra D. Lovejoy, Christopher P. Leamon, David E. Morgenstern, Richard A. Messmann

Research output: Contribution to journalArticle

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Abstract

Purpose Vintafolide (EC145) is a folic acid- desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, 99mTc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m2 intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. Results The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P < .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P < .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Conclusion Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

Original languageEnglish (US)
Pages (from-to)4400-4406
Number of pages7
JournalJournal of Clinical Oncology
Volume31
Issue number35
DOIs
StatePublished - Dec 10 2013

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Platinum
Ovarian Neoplasms
Folic Acid
Disease-Free Survival
liposomal doxorubicin
EC145
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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PRECEDENT : A randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer. / Naumann, R. Wendel; Coleman, Robert L.; Burger, Robert A.; Sausville, Edward A.; Kutarska, Elzbieta; Ghamande, Sharad A; Gabrail, Nashat Y.; DePasquale, Stephen E.; Nowara, Elzbieta; Gilbert, Lucy; Gersh, Robert H.; Teneriello, Michael G.; Harb, Wael A.; Konstantinopoulos, Panagiotis A.; Penson, Richard T.; Symanowski, James T.; Lovejoy, Chandra D.; Leamon, Christopher P.; Morgenstern, David E.; Messmann, Richard A.

In: Journal of Clinical Oncology, Vol. 31, No. 35, 10.12.2013, p. 4400-4406.

Research output: Contribution to journalArticle

Naumann, RW, Coleman, RL, Burger, RA, Sausville, EA, Kutarska, E, Ghamande, SA, Gabrail, NY, DePasquale, SE, Nowara, E, Gilbert, L, Gersh, RH, Teneriello, MG, Harb, WA, Konstantinopoulos, PA, Penson, RT, Symanowski, JT, Lovejoy, CD, Leamon, CP, Morgenstern, DE & Messmann, RA 2013, 'PRECEDENT: A randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer', Journal of Clinical Oncology, vol. 31, no. 35, pp. 4400-4406. https://doi.org/10.1200/JCO.2013.49.7685
Naumann, R. Wendel ; Coleman, Robert L. ; Burger, Robert A. ; Sausville, Edward A. ; Kutarska, Elzbieta ; Ghamande, Sharad A ; Gabrail, Nashat Y. ; DePasquale, Stephen E. ; Nowara, Elzbieta ; Gilbert, Lucy ; Gersh, Robert H. ; Teneriello, Michael G. ; Harb, Wael A. ; Konstantinopoulos, Panagiotis A. ; Penson, Richard T. ; Symanowski, James T. ; Lovejoy, Chandra D. ; Leamon, Christopher P. ; Morgenstern, David E. ; Messmann, Richard A. / PRECEDENT : A randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 35. pp. 4400-4406.
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abstract = "Purpose Vintafolide (EC145) is a folic acid- desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, 99mTc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m2 intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. Results The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95{\%} CI, 0.41 to 0.96; P < .031). The greatest benefit was observed in patients with 100{\%} of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95{\%} CI, 0.17 to 0.85; P < .013). The group of patients with FR-positive disease (10{\%} to 90{\%}) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Conclusion Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.",
author = "Naumann, {R. Wendel} and Coleman, {Robert L.} and Burger, {Robert A.} and Sausville, {Edward A.} and Elzbieta Kutarska and Ghamande, {Sharad A} and Gabrail, {Nashat Y.} and DePasquale, {Stephen E.} and Elzbieta Nowara and Lucy Gilbert and Gersh, {Robert H.} and Teneriello, {Michael G.} and Harb, {Wael A.} and Konstantinopoulos, {Panagiotis A.} and Penson, {Richard T.} and Symanowski, {James T.} and Lovejoy, {Chandra D.} and Leamon, {Christopher P.} and Morgenstern, {David E.} and Messmann, {Richard A.}",
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T2 - A randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer

AU - Naumann, R. Wendel

AU - Coleman, Robert L.

AU - Burger, Robert A.

AU - Sausville, Edward A.

AU - Kutarska, Elzbieta

AU - Ghamande, Sharad A

AU - Gabrail, Nashat Y.

AU - DePasquale, Stephen E.

AU - Nowara, Elzbieta

AU - Gilbert, Lucy

AU - Gersh, Robert H.

AU - Teneriello, Michael G.

AU - Harb, Wael A.

AU - Konstantinopoulos, Panagiotis A.

AU - Penson, Richard T.

AU - Symanowski, James T.

AU - Lovejoy, Chandra D.

AU - Leamon, Christopher P.

AU - Morgenstern, David E.

AU - Messmann, Richard A.

PY - 2013/12/10

Y1 - 2013/12/10

N2 - Purpose Vintafolide (EC145) is a folic acid- desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, 99mTc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m2 intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. Results The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P < .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P < .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Conclusion Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

AB - Purpose Vintafolide (EC145) is a folic acid- desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, 99mTc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m2 intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. Results The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P < .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P < .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Conclusion Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

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