Randomized phase II study of ramucirumab or icrucumab in combination with capecitabine in patients with previously treated locally advanced or metastatic breast cancer

Linda T. Vahdat, Rachel Layman, Denise A. Yardley, William Gradishar, Mohamad A. Salkeni, Anil Abraham Joy, Agustin A. Garcia, Patrick Ward, James Khatcheressian, Joseph A. Sparano, Gladys Rodriguez, Shande Tang, Ling Gao, Rita P. Dalal, John Kauh, Kathy Miller

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background. Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and-2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced ormetastatic breast cancer. Methods. Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg/m2 orally twice daily, days 1-14) alone or in combination with RAM (10 mg/kg intravenously [IV], days 1 and 8) (RAM1CAP) or ICR (12 mg/kg IV, days 1 and 8) (ICR1 CAP) every 21 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), tumor response, safety, and pharmacokinetics. Results. Of 153 patients randomized, 150 received treatment. Median PFS (95% confidence interval) was 22.1 (12.1-36.1) weeks on RAM1CAP, 7.3 (6.3-13.0) weeks on ICR1CAP, and 19.0 (12.1-24.3) weeks on CAP (hazard ratios [HRs]: 0.691, p5.1315, RAM1CAP versus CAP; 1.480, p5.0851, ICR1 CAP versus CAP). Median OS was 67.4 weeks on RAM1CAP, 62.1 weeks on ICR1CAP, and 71.6 weeks on CAP (HRs: 1.833, p5.0283, RAM1CAP versus CAP; 1.468, p5.1550, ICR1 CAP versus CAP). There was no statistically significant difference in PFS or OS between either combination arm and CAP. Treatment-related adverse events more frequent (by ≥ 10%) on RAM1CAP than on CAP were constipation, decreased appetite, headache, epistaxis, and hypertension. Those more frequent (by ≥ 10%) on ICR1CAP than CAP were anemia, increased lacrimation, periorbital edema, nausea, vomiting, peripheral edema, facial edema, dehydration, and dyspnea. Conclusion. Combining RAM or ICR with CAP did not improve PFS in the targeted study population.

Original languageEnglish (US)
Pages (from-to)245-254
Number of pages10
JournalOncologist
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2017

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Breast Neoplasms
Disease-Free Survival
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Edema
Capecitabine
ramucirumab
Survival
Safety
Epistaxis
Appetite
Constipation
Dehydration
Dyspnea
Nausea
Vomiting
Headache
Anemia
Pharmacokinetics
Confidence Intervals

Keywords

  • Breast cancer
  • Capecitabine
  • Drug resistance
  • Metastasis
  • Monoclonal antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Randomized phase II study of ramucirumab or icrucumab in combination with capecitabine in patients with previously treated locally advanced or metastatic breast cancer. / Vahdat, Linda T.; Layman, Rachel; Yardley, Denise A.; Gradishar, William; Salkeni, Mohamad A.; Joy, Anil Abraham; Garcia, Agustin A.; Ward, Patrick; Khatcheressian, James; Sparano, Joseph A.; Rodriguez, Gladys; Tang, Shande; Gao, Ling; Dalal, Rita P.; Kauh, John; Miller, Kathy.

In: Oncologist, Vol. 22, No. 3, 01.03.2017, p. 245-254.

Research output: Contribution to journalArticle

Vahdat, LT, Layman, R, Yardley, DA, Gradishar, W, Salkeni, MA, Joy, AA, Garcia, AA, Ward, P, Khatcheressian, J, Sparano, JA, Rodriguez, G, Tang, S, Gao, L, Dalal, RP, Kauh, J & Miller, K 2017, 'Randomized phase II study of ramucirumab or icrucumab in combination with capecitabine in patients with previously treated locally advanced or metastatic breast cancer', Oncologist, vol. 22, no. 3, pp. 245-254. https://doi.org/10.1634/theoncologist.2016-0265
Vahdat, Linda T. ; Layman, Rachel ; Yardley, Denise A. ; Gradishar, William ; Salkeni, Mohamad A. ; Joy, Anil Abraham ; Garcia, Agustin A. ; Ward, Patrick ; Khatcheressian, James ; Sparano, Joseph A. ; Rodriguez, Gladys ; Tang, Shande ; Gao, Ling ; Dalal, Rita P. ; Kauh, John ; Miller, Kathy. / Randomized phase II study of ramucirumab or icrucumab in combination with capecitabine in patients with previously treated locally advanced or metastatic breast cancer. In: Oncologist. 2017 ; Vol. 22, No. 3. pp. 245-254.
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abstract = "Background. Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and-2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced ormetastatic breast cancer. Methods. Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg/m2 orally twice daily, days 1-14) alone or in combination with RAM (10 mg/kg intravenously [IV], days 1 and 8) (RAM1CAP) or ICR (12 mg/kg IV, days 1 and 8) (ICR1 CAP) every 21 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), tumor response, safety, and pharmacokinetics. Results. Of 153 patients randomized, 150 received treatment. Median PFS (95{\%} confidence interval) was 22.1 (12.1-36.1) weeks on RAM1CAP, 7.3 (6.3-13.0) weeks on ICR1CAP, and 19.0 (12.1-24.3) weeks on CAP (hazard ratios [HRs]: 0.691, p5.1315, RAM1CAP versus CAP; 1.480, p5.0851, ICR1 CAP versus CAP). Median OS was 67.4 weeks on RAM1CAP, 62.1 weeks on ICR1CAP, and 71.6 weeks on CAP (HRs: 1.833, p5.0283, RAM1CAP versus CAP; 1.468, p5.1550, ICR1 CAP versus CAP). There was no statistically significant difference in PFS or OS between either combination arm and CAP. Treatment-related adverse events more frequent (by ≥ 10{\%}) on RAM1CAP than on CAP were constipation, decreased appetite, headache, epistaxis, and hypertension. Those more frequent (by ≥ 10{\%}) on ICR1CAP than CAP were anemia, increased lacrimation, periorbital edema, nausea, vomiting, peripheral edema, facial edema, dehydration, and dyspnea. Conclusion. Combining RAM or ICR with CAP did not improve PFS in the targeted study population.",
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T1 - Randomized phase II study of ramucirumab or icrucumab in combination with capecitabine in patients with previously treated locally advanced or metastatic breast cancer

AU - Vahdat, Linda T.

AU - Layman, Rachel

AU - Yardley, Denise A.

AU - Gradishar, William

AU - Salkeni, Mohamad A.

AU - Joy, Anil Abraham

AU - Garcia, Agustin A.

AU - Ward, Patrick

AU - Khatcheressian, James

AU - Sparano, Joseph A.

AU - Rodriguez, Gladys

AU - Tang, Shande

AU - Gao, Ling

AU - Dalal, Rita P.

AU - Kauh, John

AU - Miller, Kathy

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Background. Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and-2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced ormetastatic breast cancer. Methods. Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg/m2 orally twice daily, days 1-14) alone or in combination with RAM (10 mg/kg intravenously [IV], days 1 and 8) (RAM1CAP) or ICR (12 mg/kg IV, days 1 and 8) (ICR1 CAP) every 21 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), tumor response, safety, and pharmacokinetics. Results. Of 153 patients randomized, 150 received treatment. Median PFS (95% confidence interval) was 22.1 (12.1-36.1) weeks on RAM1CAP, 7.3 (6.3-13.0) weeks on ICR1CAP, and 19.0 (12.1-24.3) weeks on CAP (hazard ratios [HRs]: 0.691, p5.1315, RAM1CAP versus CAP; 1.480, p5.0851, ICR1 CAP versus CAP). Median OS was 67.4 weeks on RAM1CAP, 62.1 weeks on ICR1CAP, and 71.6 weeks on CAP (HRs: 1.833, p5.0283, RAM1CAP versus CAP; 1.468, p5.1550, ICR1 CAP versus CAP). There was no statistically significant difference in PFS or OS between either combination arm and CAP. Treatment-related adverse events more frequent (by ≥ 10%) on RAM1CAP than on CAP were constipation, decreased appetite, headache, epistaxis, and hypertension. Those more frequent (by ≥ 10%) on ICR1CAP than CAP were anemia, increased lacrimation, periorbital edema, nausea, vomiting, peripheral edema, facial edema, dehydration, and dyspnea. Conclusion. Combining RAM or ICR with CAP did not improve PFS in the targeted study population.

AB - Background. Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and-2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced ormetastatic breast cancer. Methods. Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg/m2 orally twice daily, days 1-14) alone or in combination with RAM (10 mg/kg intravenously [IV], days 1 and 8) (RAM1CAP) or ICR (12 mg/kg IV, days 1 and 8) (ICR1 CAP) every 21 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), tumor response, safety, and pharmacokinetics. Results. Of 153 patients randomized, 150 received treatment. Median PFS (95% confidence interval) was 22.1 (12.1-36.1) weeks on RAM1CAP, 7.3 (6.3-13.0) weeks on ICR1CAP, and 19.0 (12.1-24.3) weeks on CAP (hazard ratios [HRs]: 0.691, p5.1315, RAM1CAP versus CAP; 1.480, p5.0851, ICR1 CAP versus CAP). Median OS was 67.4 weeks on RAM1CAP, 62.1 weeks on ICR1CAP, and 71.6 weeks on CAP (HRs: 1.833, p5.0283, RAM1CAP versus CAP; 1.468, p5.1550, ICR1 CAP versus CAP). There was no statistically significant difference in PFS or OS between either combination arm and CAP. Treatment-related adverse events more frequent (by ≥ 10%) on RAM1CAP than on CAP were constipation, decreased appetite, headache, epistaxis, and hypertension. Those more frequent (by ≥ 10%) on ICR1CAP than CAP were anemia, increased lacrimation, periorbital edema, nausea, vomiting, peripheral edema, facial edema, dehydration, and dyspnea. Conclusion. Combining RAM or ICR with CAP did not improve PFS in the targeted study population.

KW - Breast cancer

KW - Capecitabine

KW - Drug resistance

KW - Metastasis

KW - Monoclonal antibodies

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