SWOG S0800 (NCI CDR0000636131): addition of bevacizumab to neoadjuvant nab-paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer

Z. A. Nahleh, W. E. Barlow, D. F. Hayes, A. F. Schott, J. R. Gralow, W. M. Sikov, E. A. Perez, S. Chennuru, H. R. Mirshahidi, S. W. Corso, D. L. Lew, L. Pusztai, Robert B Livingston, G. N. Hortobagyi

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Abstract

SWOG S0800, a randomized open-label Phase II clinical trial, compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients were randomly allocated (2:1:1) to three neoadjuvant chemotherapy arms: (1) nab-paclitaxel with concurrent bevacizumab followed by AC; (2) nab-paclitaxel followed by AC; or (3) AC followed by nab-paclitaxel. The primary endpoint was pathologic complete response (pCR) with stratification by disease type (non-IBC LABC vs. IBC) and hormone receptor status (positive vs. negative). Overall survival (OS), event-free survival (EFS), and toxicity were secondary endpoints. Analyses were intent-to-treat comparing bevacizumab to the combined control arms. A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer (TNBC). The addition of bevacizumab significantly increased the pCR rate overall (36 vs. 21 %; p = 0.019) and in TNBC (59 vs. 29 %; p = 0.014), but not in hormone receptor-positive disease (24 vs. 18 %; p = 0.41). Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate. While no significant differences in OS or EFS were seen, a trend favored the addition of bevacizumab for EFS (p = 0.06) in TNBC. Overall, Grade 3–4 adverse events did not differ substantially by treatment arm. The addition of bevacizumab to nab-paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS. This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer.

Original languageEnglish (US)
Pages (from-to)485-495
Number of pages11
JournalBreast Cancer Research and Treatment
Volume158
Issue number3
DOIs
StatePublished - Aug 1 2016

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Doxorubicin
Cyclophosphamide
Inflammatory Breast Neoplasms
Breast Neoplasms
Triple Negative Breast Neoplasms
Disease-Free Survival
Drug Therapy
Hormones
Phase II Clinical Trials
Neoadjuvant Therapy
Survival
Bevacizumab
130-nm albumin-bound paclitaxel

Keywords

  • Bevacizumab
  • Breast cancer
  • Inflammatory
  • Locally advanced
  • Neoadjuvant

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

SWOG S0800 (NCI CDR0000636131) : addition of bevacizumab to neoadjuvant nab-paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer. / Nahleh, Z. A.; Barlow, W. E.; Hayes, D. F.; Schott, A. F.; Gralow, J. R.; Sikov, W. M.; Perez, E. A.; Chennuru, S.; Mirshahidi, H. R.; Corso, S. W.; Lew, D. L.; Pusztai, L.; Livingston, Robert B; Hortobagyi, G. N.

In: Breast Cancer Research and Treatment, Vol. 158, No. 3, 01.08.2016, p. 485-495.

Research output: Contribution to journalArticle

Nahleh, Z. A. ; Barlow, W. E. ; Hayes, D. F. ; Schott, A. F. ; Gralow, J. R. ; Sikov, W. M. ; Perez, E. A. ; Chennuru, S. ; Mirshahidi, H. R. ; Corso, S. W. ; Lew, D. L. ; Pusztai, L. ; Livingston, Robert B ; Hortobagyi, G. N. / SWOG S0800 (NCI CDR0000636131) : addition of bevacizumab to neoadjuvant nab-paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer. In: Breast Cancer Research and Treatment. 2016 ; Vol. 158, No. 3. pp. 485-495.
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abstract = "SWOG S0800, a randomized open-label Phase II clinical trial, compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients were randomly allocated (2:1:1) to three neoadjuvant chemotherapy arms: (1) nab-paclitaxel with concurrent bevacizumab followed by AC; (2) nab-paclitaxel followed by AC; or (3) AC followed by nab-paclitaxel. The primary endpoint was pathologic complete response (pCR) with stratification by disease type (non-IBC LABC vs. IBC) and hormone receptor status (positive vs. negative). Overall survival (OS), event-free survival (EFS), and toxicity were secondary endpoints. Analyses were intent-to-treat comparing bevacizumab to the combined control arms. A total of 215 patients were accrued including 11 {\%} with IBC and 32 {\%} with triple-negative breast cancer (TNBC). The addition of bevacizumab significantly increased the pCR rate overall (36 vs. 21 {\%}; p = 0.019) and in TNBC (59 vs. 29 {\%}; p = 0.014), but not in hormone receptor-positive disease (24 vs. 18 {\%}; p = 0.41). Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate. While no significant differences in OS or EFS were seen, a trend favored the addition of bevacizumab for EFS (p = 0.06) in TNBC. Overall, Grade 3–4 adverse events did not differ substantially by treatment arm. The addition of bevacizumab to nab-paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS. This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer.",
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AU - Nahleh, Z. A.

AU - Barlow, W. E.

AU - Hayes, D. F.

AU - Schott, A. F.

AU - Gralow, J. R.

AU - Sikov, W. M.

AU - Perez, E. A.

AU - Chennuru, S.

AU - Mirshahidi, H. R.

AU - Corso, S. W.

AU - Lew, D. L.

AU - Pusztai, L.

AU - Livingston, Robert B

AU - Hortobagyi, G. N.

PY - 2016/8/1

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N2 - SWOG S0800, a randomized open-label Phase II clinical trial, compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients were randomly allocated (2:1:1) to three neoadjuvant chemotherapy arms: (1) nab-paclitaxel with concurrent bevacizumab followed by AC; (2) nab-paclitaxel followed by AC; or (3) AC followed by nab-paclitaxel. The primary endpoint was pathologic complete response (pCR) with stratification by disease type (non-IBC LABC vs. IBC) and hormone receptor status (positive vs. negative). Overall survival (OS), event-free survival (EFS), and toxicity were secondary endpoints. Analyses were intent-to-treat comparing bevacizumab to the combined control arms. A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer (TNBC). The addition of bevacizumab significantly increased the pCR rate overall (36 vs. 21 %; p = 0.019) and in TNBC (59 vs. 29 %; p = 0.014), but not in hormone receptor-positive disease (24 vs. 18 %; p = 0.41). Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate. While no significant differences in OS or EFS were seen, a trend favored the addition of bevacizumab for EFS (p = 0.06) in TNBC. Overall, Grade 3–4 adverse events did not differ substantially by treatment arm. The addition of bevacizumab to nab-paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS. This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer.

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