A randomized phase II study of paclitaxel and bevacizumab with and without gemcitabine as first-line treatment for metastatic breast cancer

Adam Brufsky, Karen Hoelzer, Thaddeus Beck, Robert Whorf, Mark Keaton, Padma Nadella, Elisa Krill-Jackson, Joan Kroener, Edward Middleman, Michael Frontiera, Devchand Paul, Timothy Panella, Jane Bromund, Luping Zhao, Mauro Orlando, Fritz Tai, Martin D. Marciniak, Coleman Obasaju, John Hainsworth

Research output: Contribution to journalArticle

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Abstract

Background: The addition of bevacizumab to paclitaxel improved progression-free survival (PFS) of patients with metastatic breast cancer (MBC). We examined the efficacy and safety of adding gemcitabine to paclitaxel/bevacizumab (PB). Patients and Methods: In this multicenter, open-label, randomized phase II trial, women with locally advanced or MBC were randomly assigned to receive paclitaxel 90 mg/m2 (days 1, 8, 15) and bevacizumab 10 mg/kg (days 1, 15) with or without gemcitabine 1500 mg/m 2 (days 1, 15) in 28-day cycles. Patients with prior cytotoxic therapy for MBC were ineligible. The primary endpoint was investigator-assessed overall response rate (ORR); secondary endpoints were PFS, overall survival (OS), safety, and quality of life. Results: Ninety-four patients received PB, and 93 received paclitaxel/bevacizumab/gemcitabine (PB+G). The ORRs were 48.9% (95% confidence interval [CI], 38.5%-59.5%) and 58.7% (95% CI, 47.9%-68.9%; P =.117) with PB and PB+G, respectively. The median PFS was 8.8 months (95% CI, 8.1-10.4 months) and 11.3 months (95% CI, 9.7-12.7 months; P =.247; hazard ratio, 0.82); the median OS was 25.0 months (95% CI, 18.8-not assessable [N/A] months) and 24.3 months (95% CI, 20.3-N/A months; P =.475; hazard ratio, 0.84), with PB and PB+G, respectively. There was significantly more grade 3-4 neutropenia (P =.001) and dyspnea (P =.014) with PB+G. Patients treated with PB experienced more improvement in total FACT-B (Functional Assessment of Cancer Therapy-Breast) (P =.021), FACT-B Social/Family Well-being (P =.041), and Breast Cancer-Additional Concerns (P =.008) scores than patients treated with PB+G. Conclusion: The addition of gemcitabine to PB was not associated with a statistically significant improvement in ORR. Treatment with PB+G increased the incidence of severe neutropenia and dyspnea, although the regimen generally was well tolerated.

Original languageEnglish (US)
Pages (from-to)211-220
Number of pages10
JournalClinical Breast Cancer
Volume11
Issue number4
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

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gemcitabine
Paclitaxel
Breast Neoplasms
Confidence Intervals
Therapeutics
Disease-Free Survival
Bevacizumab
Neutropenia
Dyspnea

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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A randomized phase II study of paclitaxel and bevacizumab with and without gemcitabine as first-line treatment for metastatic breast cancer. / Brufsky, Adam; Hoelzer, Karen; Beck, Thaddeus; Whorf, Robert; Keaton, Mark; Nadella, Padma; Krill-Jackson, Elisa; Kroener, Joan; Middleman, Edward; Frontiera, Michael; Paul, Devchand; Panella, Timothy; Bromund, Jane; Zhao, Luping; Orlando, Mauro; Tai, Fritz; Marciniak, Martin D.; Obasaju, Coleman; Hainsworth, John.

In: Clinical Breast Cancer, Vol. 11, No. 4, 01.01.2011, p. 211-220.

Research output: Contribution to journalArticle

Brufsky, A, Hoelzer, K, Beck, T, Whorf, R, Keaton, M, Nadella, P, Krill-Jackson, E, Kroener, J, Middleman, E, Frontiera, M, Paul, D, Panella, T, Bromund, J, Zhao, L, Orlando, M, Tai, F, Marciniak, MD, Obasaju, C & Hainsworth, J 2011, 'A randomized phase II study of paclitaxel and bevacizumab with and without gemcitabine as first-line treatment for metastatic breast cancer', Clinical Breast Cancer, vol. 11, no. 4, pp. 211-220. https://doi.org/10.1016/j.clbc.2011.03.019
Brufsky, Adam ; Hoelzer, Karen ; Beck, Thaddeus ; Whorf, Robert ; Keaton, Mark ; Nadella, Padma ; Krill-Jackson, Elisa ; Kroener, Joan ; Middleman, Edward ; Frontiera, Michael ; Paul, Devchand ; Panella, Timothy ; Bromund, Jane ; Zhao, Luping ; Orlando, Mauro ; Tai, Fritz ; Marciniak, Martin D. ; Obasaju, Coleman ; Hainsworth, John. / A randomized phase II study of paclitaxel and bevacizumab with and without gemcitabine as first-line treatment for metastatic breast cancer. In: Clinical Breast Cancer. 2011 ; Vol. 11, No. 4. pp. 211-220.
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abstract = "Background: The addition of bevacizumab to paclitaxel improved progression-free survival (PFS) of patients with metastatic breast cancer (MBC). We examined the efficacy and safety of adding gemcitabine to paclitaxel/bevacizumab (PB). Patients and Methods: In this multicenter, open-label, randomized phase II trial, women with locally advanced or MBC were randomly assigned to receive paclitaxel 90 mg/m2 (days 1, 8, 15) and bevacizumab 10 mg/kg (days 1, 15) with or without gemcitabine 1500 mg/m 2 (days 1, 15) in 28-day cycles. Patients with prior cytotoxic therapy for MBC were ineligible. The primary endpoint was investigator-assessed overall response rate (ORR); secondary endpoints were PFS, overall survival (OS), safety, and quality of life. Results: Ninety-four patients received PB, and 93 received paclitaxel/bevacizumab/gemcitabine (PB+G). The ORRs were 48.9{\%} (95{\%} confidence interval [CI], 38.5{\%}-59.5{\%}) and 58.7{\%} (95{\%} CI, 47.9{\%}-68.9{\%}; P =.117) with PB and PB+G, respectively. The median PFS was 8.8 months (95{\%} CI, 8.1-10.4 months) and 11.3 months (95{\%} CI, 9.7-12.7 months; P =.247; hazard ratio, 0.82); the median OS was 25.0 months (95{\%} CI, 18.8-not assessable [N/A] months) and 24.3 months (95{\%} CI, 20.3-N/A months; P =.475; hazard ratio, 0.84), with PB and PB+G, respectively. There was significantly more grade 3-4 neutropenia (P =.001) and dyspnea (P =.014) with PB+G. Patients treated with PB experienced more improvement in total FACT-B (Functional Assessment of Cancer Therapy-Breast) (P =.021), FACT-B Social/Family Well-being (P =.041), and Breast Cancer-Additional Concerns (P =.008) scores than patients treated with PB+G. Conclusion: The addition of gemcitabine to PB was not associated with a statistically significant improvement in ORR. Treatment with PB+G increased the incidence of severe neutropenia and dyspnea, although the regimen generally was well tolerated.",
author = "Adam Brufsky and Karen Hoelzer and Thaddeus Beck and Robert Whorf and Mark Keaton and Padma Nadella and Elisa Krill-Jackson and Joan Kroener and Edward Middleman and Michael Frontiera and Devchand Paul and Timothy Panella and Jane Bromund and Luping Zhao and Mauro Orlando and Fritz Tai and Marciniak, {Martin D.} and Coleman Obasaju and John Hainsworth",
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T1 - A randomized phase II study of paclitaxel and bevacizumab with and without gemcitabine as first-line treatment for metastatic breast cancer

AU - Brufsky, Adam

AU - Hoelzer, Karen

AU - Beck, Thaddeus

AU - Whorf, Robert

AU - Keaton, Mark

AU - Nadella, Padma

AU - Krill-Jackson, Elisa

AU - Kroener, Joan

AU - Middleman, Edward

AU - Frontiera, Michael

AU - Paul, Devchand

AU - Panella, Timothy

AU - Bromund, Jane

AU - Zhao, Luping

AU - Orlando, Mauro

AU - Tai, Fritz

AU - Marciniak, Martin D.

AU - Obasaju, Coleman

AU - Hainsworth, John

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Background: The addition of bevacizumab to paclitaxel improved progression-free survival (PFS) of patients with metastatic breast cancer (MBC). We examined the efficacy and safety of adding gemcitabine to paclitaxel/bevacizumab (PB). Patients and Methods: In this multicenter, open-label, randomized phase II trial, women with locally advanced or MBC were randomly assigned to receive paclitaxel 90 mg/m2 (days 1, 8, 15) and bevacizumab 10 mg/kg (days 1, 15) with or without gemcitabine 1500 mg/m 2 (days 1, 15) in 28-day cycles. Patients with prior cytotoxic therapy for MBC were ineligible. The primary endpoint was investigator-assessed overall response rate (ORR); secondary endpoints were PFS, overall survival (OS), safety, and quality of life. Results: Ninety-four patients received PB, and 93 received paclitaxel/bevacizumab/gemcitabine (PB+G). The ORRs were 48.9% (95% confidence interval [CI], 38.5%-59.5%) and 58.7% (95% CI, 47.9%-68.9%; P =.117) with PB and PB+G, respectively. The median PFS was 8.8 months (95% CI, 8.1-10.4 months) and 11.3 months (95% CI, 9.7-12.7 months; P =.247; hazard ratio, 0.82); the median OS was 25.0 months (95% CI, 18.8-not assessable [N/A] months) and 24.3 months (95% CI, 20.3-N/A months; P =.475; hazard ratio, 0.84), with PB and PB+G, respectively. There was significantly more grade 3-4 neutropenia (P =.001) and dyspnea (P =.014) with PB+G. Patients treated with PB experienced more improvement in total FACT-B (Functional Assessment of Cancer Therapy-Breast) (P =.021), FACT-B Social/Family Well-being (P =.041), and Breast Cancer-Additional Concerns (P =.008) scores than patients treated with PB+G. Conclusion: The addition of gemcitabine to PB was not associated with a statistically significant improvement in ORR. Treatment with PB+G increased the incidence of severe neutropenia and dyspnea, although the regimen generally was well tolerated.

AB - Background: The addition of bevacizumab to paclitaxel improved progression-free survival (PFS) of patients with metastatic breast cancer (MBC). We examined the efficacy and safety of adding gemcitabine to paclitaxel/bevacizumab (PB). Patients and Methods: In this multicenter, open-label, randomized phase II trial, women with locally advanced or MBC were randomly assigned to receive paclitaxel 90 mg/m2 (days 1, 8, 15) and bevacizumab 10 mg/kg (days 1, 15) with or without gemcitabine 1500 mg/m 2 (days 1, 15) in 28-day cycles. Patients with prior cytotoxic therapy for MBC were ineligible. The primary endpoint was investigator-assessed overall response rate (ORR); secondary endpoints were PFS, overall survival (OS), safety, and quality of life. Results: Ninety-four patients received PB, and 93 received paclitaxel/bevacizumab/gemcitabine (PB+G). The ORRs were 48.9% (95% confidence interval [CI], 38.5%-59.5%) and 58.7% (95% CI, 47.9%-68.9%; P =.117) with PB and PB+G, respectively. The median PFS was 8.8 months (95% CI, 8.1-10.4 months) and 11.3 months (95% CI, 9.7-12.7 months; P =.247; hazard ratio, 0.82); the median OS was 25.0 months (95% CI, 18.8-not assessable [N/A] months) and 24.3 months (95% CI, 20.3-N/A months; P =.475; hazard ratio, 0.84), with PB and PB+G, respectively. There was significantly more grade 3-4 neutropenia (P =.001) and dyspnea (P =.014) with PB+G. Patients treated with PB experienced more improvement in total FACT-B (Functional Assessment of Cancer Therapy-Breast) (P =.021), FACT-B Social/Family Well-being (P =.041), and Breast Cancer-Additional Concerns (P =.008) scores than patients treated with PB+G. Conclusion: The addition of gemcitabine to PB was not associated with a statistically significant improvement in ORR. Treatment with PB+G increased the incidence of severe neutropenia and dyspnea, although the regimen generally was well tolerated.

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