Intravenous aflibercept in patients with platinum-resistant, advanced ovarian cancer: Results of a randomized, double-blind, phase 2, parallel-arm study

William P. Tew, Nicoletta Colombo, Isabelle Ray-Coquard, Josep M. Del Campo, Amit Oza, Deolinda Pereira, Serafina Mammoliti, Daniela Matei, Giovanni Scambia, Katia Tonkin, Zhenming Shun, Lars Sternas, David R. Spriggs

Research output: Contribution to journalArticle

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Abstract

Background In this randomized phase 2 study, the authors assessed the efficacy and safety of intravenous aflibercept at 2 different doses (2 mg/kg or 4 mg/kg) in patients with recurrent, platinum-resistant ovarian, peritoneal, or fallopian tube cancer who developed disease progression after receiving topotecan and/or pegylated liposomal doxorubicin. Methods Patients were randomized to receive intravenous aflibercept at a dose of either 2 mg/kg or 4 mg/kg every 2 weeks until they developed disease progression or significant toxicity. The primary endpoint was to evaluate Response Evaluation Criteria in Solid Tumor response rates (overall response rate [ORR] = complete responses plus partial responses) and to test the null hypothesis (ORR, >5%). Secondary endpoints included time to tumor progression, safety, progression-free survival/overall survival, drug pharmacokinetics, and immunogenicity. In total, 67 evaluable patients per cohort were planned based on a Simon 2-stage design, and, if those patients responded, then enrollment could extend to 200 patients. Tumor radiographic response was assessed by investigators and by an independent review committee. Results After the first 84 evaluable patients, 8 unconfirmed partial responders were noted (ORR, 10%) across both arms; the Independent Data Monitoring Committee recommended continuing blinded accrual. At study completion, 215 evaluable patients were accrued, including 1 responder of 106 patients (0.9%) in the 2-mg/kg cohort and 5 responders of 109 patients (4.6%) in the 4-mg/kg cohort according to the independent review committee. The clinical benefit rate (ORR plus stable disease >6 months) was 12.3% and 11% in the 2-mg/kg and 4-mg/kg cohorts, respectively. Treatment-related grade 3 and 4 adverse events included hypertension (25.5% and 27.5% in the 2-mg/kg and 4-mg/kg cohorts, respectively), proteinuria (9.4% and 7.3%, respectively), and fatigue (5.7% and 3.7%, respectively). The gastrointestinal perforation rate was low (3 patients; 1.4%). Conclusions Aflibercept at a dose of either 2 mg/kg or 4 mg/kg was generally well tolerated but did not meet the primary endpoint for response.

Original languageEnglish
Pages (from-to)335-343
Number of pages9
JournalCancer
Volume120
Issue number3
DOIs
StatePublished - Feb 1 2014

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Platinum
Ovarian Neoplasms
Advisory Committees
Disease Progression
Fallopian Tube Neoplasms
Clinical Trials Data Monitoring Committees
aflibercept
Topotecan
Safety
Proteinuria
Disease-Free Survival
Fatigue
Neoplasms
Pharmacokinetics
Research Personnel
Hypertension
Survival

Keywords

  • advanced stage
  • aflibercept
  • ovarian cancer
  • phase 2
  • platinum resistance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tew, W. P., Colombo, N., Ray-Coquard, I., Del Campo, J. M., Oza, A., Pereira, D., ... Spriggs, D. R. (2014). Intravenous aflibercept in patients with platinum-resistant, advanced ovarian cancer: Results of a randomized, double-blind, phase 2, parallel-arm study. Cancer, 120(3), 335-343. https://doi.org/10.1002/cncr.28406

Intravenous aflibercept in patients with platinum-resistant, advanced ovarian cancer : Results of a randomized, double-blind, phase 2, parallel-arm study. / Tew, William P.; Colombo, Nicoletta; Ray-Coquard, Isabelle; Del Campo, Josep M.; Oza, Amit; Pereira, Deolinda; Mammoliti, Serafina; Matei, Daniela; Scambia, Giovanni; Tonkin, Katia; Shun, Zhenming; Sternas, Lars; Spriggs, David R.

In: Cancer, Vol. 120, No. 3, 01.02.2014, p. 335-343.

Research output: Contribution to journalArticle

Tew, WP, Colombo, N, Ray-Coquard, I, Del Campo, JM, Oza, A, Pereira, D, Mammoliti, S, Matei, D, Scambia, G, Tonkin, K, Shun, Z, Sternas, L & Spriggs, DR 2014, 'Intravenous aflibercept in patients with platinum-resistant, advanced ovarian cancer: Results of a randomized, double-blind, phase 2, parallel-arm study', Cancer, vol. 120, no. 3, pp. 335-343. https://doi.org/10.1002/cncr.28406
Tew, William P. ; Colombo, Nicoletta ; Ray-Coquard, Isabelle ; Del Campo, Josep M. ; Oza, Amit ; Pereira, Deolinda ; Mammoliti, Serafina ; Matei, Daniela ; Scambia, Giovanni ; Tonkin, Katia ; Shun, Zhenming ; Sternas, Lars ; Spriggs, David R. / Intravenous aflibercept in patients with platinum-resistant, advanced ovarian cancer : Results of a randomized, double-blind, phase 2, parallel-arm study. In: Cancer. 2014 ; Vol. 120, No. 3. pp. 335-343.
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abstract = "Background In this randomized phase 2 study, the authors assessed the efficacy and safety of intravenous aflibercept at 2 different doses (2 mg/kg or 4 mg/kg) in patients with recurrent, platinum-resistant ovarian, peritoneal, or fallopian tube cancer who developed disease progression after receiving topotecan and/or pegylated liposomal doxorubicin. Methods Patients were randomized to receive intravenous aflibercept at a dose of either 2 mg/kg or 4 mg/kg every 2 weeks until they developed disease progression or significant toxicity. The primary endpoint was to evaluate Response Evaluation Criteria in Solid Tumor response rates (overall response rate [ORR] = complete responses plus partial responses) and to test the null hypothesis (ORR, >5{\%}). Secondary endpoints included time to tumor progression, safety, progression-free survival/overall survival, drug pharmacokinetics, and immunogenicity. In total, 67 evaluable patients per cohort were planned based on a Simon 2-stage design, and, if those patients responded, then enrollment could extend to 200 patients. Tumor radiographic response was assessed by investigators and by an independent review committee. Results After the first 84 evaluable patients, 8 unconfirmed partial responders were noted (ORR, 10{\%}) across both arms; the Independent Data Monitoring Committee recommended continuing blinded accrual. At study completion, 215 evaluable patients were accrued, including 1 responder of 106 patients (0.9{\%}) in the 2-mg/kg cohort and 5 responders of 109 patients (4.6{\%}) in the 4-mg/kg cohort according to the independent review committee. The clinical benefit rate (ORR plus stable disease >6 months) was 12.3{\%} and 11{\%} in the 2-mg/kg and 4-mg/kg cohorts, respectively. Treatment-related grade 3 and 4 adverse events included hypertension (25.5{\%} and 27.5{\%} in the 2-mg/kg and 4-mg/kg cohorts, respectively), proteinuria (9.4{\%} and 7.3{\%}, respectively), and fatigue (5.7{\%} and 3.7{\%}, respectively). The gastrointestinal perforation rate was low (3 patients; 1.4{\%}). Conclusions Aflibercept at a dose of either 2 mg/kg or 4 mg/kg was generally well tolerated but did not meet the primary endpoint for response.",
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T2 - Results of a randomized, double-blind, phase 2, parallel-arm study

AU - Tew, William P.

AU - Colombo, Nicoletta

AU - Ray-Coquard, Isabelle

AU - Del Campo, Josep M.

AU - Oza, Amit

AU - Pereira, Deolinda

AU - Mammoliti, Serafina

AU - Matei, Daniela

AU - Scambia, Giovanni

AU - Tonkin, Katia

AU - Shun, Zhenming

AU - Sternas, Lars

AU - Spriggs, David R.

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Background In this randomized phase 2 study, the authors assessed the efficacy and safety of intravenous aflibercept at 2 different doses (2 mg/kg or 4 mg/kg) in patients with recurrent, platinum-resistant ovarian, peritoneal, or fallopian tube cancer who developed disease progression after receiving topotecan and/or pegylated liposomal doxorubicin. Methods Patients were randomized to receive intravenous aflibercept at a dose of either 2 mg/kg or 4 mg/kg every 2 weeks until they developed disease progression or significant toxicity. The primary endpoint was to evaluate Response Evaluation Criteria in Solid Tumor response rates (overall response rate [ORR] = complete responses plus partial responses) and to test the null hypothesis (ORR, >5%). Secondary endpoints included time to tumor progression, safety, progression-free survival/overall survival, drug pharmacokinetics, and immunogenicity. In total, 67 evaluable patients per cohort were planned based on a Simon 2-stage design, and, if those patients responded, then enrollment could extend to 200 patients. Tumor radiographic response was assessed by investigators and by an independent review committee. Results After the first 84 evaluable patients, 8 unconfirmed partial responders were noted (ORR, 10%) across both arms; the Independent Data Monitoring Committee recommended continuing blinded accrual. At study completion, 215 evaluable patients were accrued, including 1 responder of 106 patients (0.9%) in the 2-mg/kg cohort and 5 responders of 109 patients (4.6%) in the 4-mg/kg cohort according to the independent review committee. The clinical benefit rate (ORR plus stable disease >6 months) was 12.3% and 11% in the 2-mg/kg and 4-mg/kg cohorts, respectively. Treatment-related grade 3 and 4 adverse events included hypertension (25.5% and 27.5% in the 2-mg/kg and 4-mg/kg cohorts, respectively), proteinuria (9.4% and 7.3%, respectively), and fatigue (5.7% and 3.7%, respectively). The gastrointestinal perforation rate was low (3 patients; 1.4%). Conclusions Aflibercept at a dose of either 2 mg/kg or 4 mg/kg was generally well tolerated but did not meet the primary endpoint for response.

AB - Background In this randomized phase 2 study, the authors assessed the efficacy and safety of intravenous aflibercept at 2 different doses (2 mg/kg or 4 mg/kg) in patients with recurrent, platinum-resistant ovarian, peritoneal, or fallopian tube cancer who developed disease progression after receiving topotecan and/or pegylated liposomal doxorubicin. Methods Patients were randomized to receive intravenous aflibercept at a dose of either 2 mg/kg or 4 mg/kg every 2 weeks until they developed disease progression or significant toxicity. The primary endpoint was to evaluate Response Evaluation Criteria in Solid Tumor response rates (overall response rate [ORR] = complete responses plus partial responses) and to test the null hypothesis (ORR, >5%). Secondary endpoints included time to tumor progression, safety, progression-free survival/overall survival, drug pharmacokinetics, and immunogenicity. In total, 67 evaluable patients per cohort were planned based on a Simon 2-stage design, and, if those patients responded, then enrollment could extend to 200 patients. Tumor radiographic response was assessed by investigators and by an independent review committee. Results After the first 84 evaluable patients, 8 unconfirmed partial responders were noted (ORR, 10%) across both arms; the Independent Data Monitoring Committee recommended continuing blinded accrual. At study completion, 215 evaluable patients were accrued, including 1 responder of 106 patients (0.9%) in the 2-mg/kg cohort and 5 responders of 109 patients (4.6%) in the 4-mg/kg cohort according to the independent review committee. The clinical benefit rate (ORR plus stable disease >6 months) was 12.3% and 11% in the 2-mg/kg and 4-mg/kg cohorts, respectively. Treatment-related grade 3 and 4 adverse events included hypertension (25.5% and 27.5% in the 2-mg/kg and 4-mg/kg cohorts, respectively), proteinuria (9.4% and 7.3%, respectively), and fatigue (5.7% and 3.7%, respectively). The gastrointestinal perforation rate was low (3 patients; 1.4%). Conclusions Aflibercept at a dose of either 2 mg/kg or 4 mg/kg was generally well tolerated but did not meet the primary endpoint for response.

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