Phase II Trial of Bevacizumab Plus Weekly Paclitaxel, Carboplatin, and Metronomic Cyclophosphamide With or Without Trastuzumab and Endocrine Therapy as Preoperative Treatment of Inflammatory Breast Cancer

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Abstract

Inflammatory breast cancer is a rare and highly aggressive disease. We investigated in a phase II study a neoadjuvant regimen with chemotherapy and an antiangiogenic strategy. The pathologic complete remission (pCR) rate was 29% and was significantly greater in patients with HER2+ tumors (57%). The achievement of a pCR was associated with longer disease-free and overall survival. The investigated regimen was effective and well tolerated. The antiangiogenic strategy warrants further studies in this setting. Background: Inflammatory breast cancer (IBC) is a rare and highly aggressive disease. A neoadjuvant regimen with chemotherapy and an antiangiogenic strategy was investigated. Patients and Methods: Patients with primary or recurrent IBC who were candidates for neoadjuvant treatment received weekly carboplatin and paclitaxel plus bevacizumab every 3 weeks and oral metronomic cyclophosphamide for 6 months. Trastuzumab was added for patients with HER2+ tumors and endocrine therapy was added for patients with estrogen receptor and/or progesterone receptor ≥ 10% tumors. Oral metronomic capecitabine and cyclophosphamide was continued for 6 months after surgery in those patients with a response. The primary efficacy endpoints were pathologic complete remission (pCR) and the objective response. Results: From July 2010 to December 2013, 34 patients with IBC were included. The surrogate intrinsic tumor subtypes were as follows: luminal B-like (HER2), 10 (29%); luminal B-like (HER2+), 8 (24%); HER2+ (nonluminal), 6 (18%); and triple negative, 10 (29%). An objective response was obtained in 30 patients (88%; 95% confidence interval, 73%-97%) and a pCR in 10 patients (29%; 95% confidence interval, 15%-48%). The proportion of pCR was significantly greater in the patients with HER2+ tumors (57%) than in patients with triple-negative (20%) or luminal B-like (HER2) tumors (0%; P =.019). After a median follow-up of 4.4 years, the 5-year disease-free survival and overall survival was 58% and 72%, respectively. The achievement of pCR was associated with longer disease-free (P =.12) and overall (P =.029) survival. Conclusion: In patients with IBC, neoadjuvant treatment with the investigated regimen was successful and well tolerated. Further studies evaluating the potential benefit of an antiangiogenic strategy in this setting are awaited.

Original languageEnglish
Pages (from-to)328-335
Number of pages8
JournalClinical Breast Cancer
Volume18
Issue number4
DOIs
Publication statusPublished - Aug 1 2018

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Inflammatory Breast Neoplasms
Carboplatin
Paclitaxel
Cyclophosphamide
Therapeutics
Neoplasms
Neoadjuvant Therapy
Disease-Free Survival
Trastuzumab
Bevacizumab
Confidence Intervals
Drug Therapy
Survival
Progesterone Receptors
Estrogen Receptors

Keywords

  • Antiangiogenesis
  • IBC
  • Metronomic chemotherapy
  • Neoadjuvant chemotherapy
  • Outcome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{5ac93dbfc0384c758b3fbbc36b0cdb3b,
title = "Phase II Trial of Bevacizumab Plus Weekly Paclitaxel, Carboplatin, and Metronomic Cyclophosphamide With or Without Trastuzumab and Endocrine Therapy as Preoperative Treatment of Inflammatory Breast Cancer",
abstract = "Inflammatory breast cancer is a rare and highly aggressive disease. We investigated in a phase II study a neoadjuvant regimen with chemotherapy and an antiangiogenic strategy. The pathologic complete remission (pCR) rate was 29{\%} and was significantly greater in patients with HER2+ tumors (57{\%}). The achievement of a pCR was associated with longer disease-free and overall survival. The investigated regimen was effective and well tolerated. The antiangiogenic strategy warrants further studies in this setting. Background: Inflammatory breast cancer (IBC) is a rare and highly aggressive disease. A neoadjuvant regimen with chemotherapy and an antiangiogenic strategy was investigated. Patients and Methods: Patients with primary or recurrent IBC who were candidates for neoadjuvant treatment received weekly carboplatin and paclitaxel plus bevacizumab every 3 weeks and oral metronomic cyclophosphamide for 6 months. Trastuzumab was added for patients with HER2+ tumors and endocrine therapy was added for patients with estrogen receptor and/or progesterone receptor ≥ 10{\%} tumors. Oral metronomic capecitabine and cyclophosphamide was continued for 6 months after surgery in those patients with a response. The primary efficacy endpoints were pathologic complete remission (pCR) and the objective response. Results: From July 2010 to December 2013, 34 patients with IBC were included. The surrogate intrinsic tumor subtypes were as follows: luminal B-like (HER2−), 10 (29{\%}); luminal B-like (HER2+), 8 (24{\%}); HER2+ (nonluminal), 6 (18{\%}); and triple negative, 10 (29{\%}). An objective response was obtained in 30 patients (88{\%}; 95{\%} confidence interval, 73{\%}-97{\%}) and a pCR in 10 patients (29{\%}; 95{\%} confidence interval, 15{\%}-48{\%}). The proportion of pCR was significantly greater in the patients with HER2+ tumors (57{\%}) than in patients with triple-negative (20{\%}) or luminal B-like (HER2−) tumors (0{\%}; P =.019). After a median follow-up of 4.4 years, the 5-year disease-free survival and overall survival was 58{\%} and 72{\%}, respectively. The achievement of pCR was associated with longer disease-free (P =.12) and overall (P =.029) survival. Conclusion: In patients with IBC, neoadjuvant treatment with the investigated regimen was successful and well tolerated. Further studies evaluating the potential benefit of an antiangiogenic strategy in this setting are awaited.",
keywords = "Antiangiogenesis, IBC, Metronomic chemotherapy, Neoadjuvant chemotherapy, Outcome",
author = "Antonella Palazzo and Silvia Dellapasqua and Elisabetta Munzone and Vincenzo Bagnardi and Manuelita Mazza and Giuseppe Cancello and Raffaella Ghisini and Monica Iorfida and Emilia Montagna and Aaron Goldhirsch and Marco Colleoni",
year = "2018",
month = "8",
day = "1",
doi = "10.1016/j.clbc.2018.01.010",
language = "English",
volume = "18",
pages = "328--335",
journal = "Clinical Breast Cancer",
issn = "1526-8209",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Phase II Trial of Bevacizumab Plus Weekly Paclitaxel, Carboplatin, and Metronomic Cyclophosphamide With or Without Trastuzumab and Endocrine Therapy as Preoperative Treatment of Inflammatory Breast Cancer

AU - Palazzo, Antonella

AU - Dellapasqua, Silvia

AU - Munzone, Elisabetta

AU - Bagnardi, Vincenzo

AU - Mazza, Manuelita

AU - Cancello, Giuseppe

AU - Ghisini, Raffaella

AU - Iorfida, Monica

AU - Montagna, Emilia

AU - Goldhirsch, Aaron

AU - Colleoni, Marco

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Inflammatory breast cancer is a rare and highly aggressive disease. We investigated in a phase II study a neoadjuvant regimen with chemotherapy and an antiangiogenic strategy. The pathologic complete remission (pCR) rate was 29% and was significantly greater in patients with HER2+ tumors (57%). The achievement of a pCR was associated with longer disease-free and overall survival. The investigated regimen was effective and well tolerated. The antiangiogenic strategy warrants further studies in this setting. Background: Inflammatory breast cancer (IBC) is a rare and highly aggressive disease. A neoadjuvant regimen with chemotherapy and an antiangiogenic strategy was investigated. Patients and Methods: Patients with primary or recurrent IBC who were candidates for neoadjuvant treatment received weekly carboplatin and paclitaxel plus bevacizumab every 3 weeks and oral metronomic cyclophosphamide for 6 months. Trastuzumab was added for patients with HER2+ tumors and endocrine therapy was added for patients with estrogen receptor and/or progesterone receptor ≥ 10% tumors. Oral metronomic capecitabine and cyclophosphamide was continued for 6 months after surgery in those patients with a response. The primary efficacy endpoints were pathologic complete remission (pCR) and the objective response. Results: From July 2010 to December 2013, 34 patients with IBC were included. The surrogate intrinsic tumor subtypes were as follows: luminal B-like (HER2−), 10 (29%); luminal B-like (HER2+), 8 (24%); HER2+ (nonluminal), 6 (18%); and triple negative, 10 (29%). An objective response was obtained in 30 patients (88%; 95% confidence interval, 73%-97%) and a pCR in 10 patients (29%; 95% confidence interval, 15%-48%). The proportion of pCR was significantly greater in the patients with HER2+ tumors (57%) than in patients with triple-negative (20%) or luminal B-like (HER2−) tumors (0%; P =.019). After a median follow-up of 4.4 years, the 5-year disease-free survival and overall survival was 58% and 72%, respectively. The achievement of pCR was associated with longer disease-free (P =.12) and overall (P =.029) survival. Conclusion: In patients with IBC, neoadjuvant treatment with the investigated regimen was successful and well tolerated. Further studies evaluating the potential benefit of an antiangiogenic strategy in this setting are awaited.

AB - Inflammatory breast cancer is a rare and highly aggressive disease. We investigated in a phase II study a neoadjuvant regimen with chemotherapy and an antiangiogenic strategy. The pathologic complete remission (pCR) rate was 29% and was significantly greater in patients with HER2+ tumors (57%). The achievement of a pCR was associated with longer disease-free and overall survival. The investigated regimen was effective and well tolerated. The antiangiogenic strategy warrants further studies in this setting. Background: Inflammatory breast cancer (IBC) is a rare and highly aggressive disease. A neoadjuvant regimen with chemotherapy and an antiangiogenic strategy was investigated. Patients and Methods: Patients with primary or recurrent IBC who were candidates for neoadjuvant treatment received weekly carboplatin and paclitaxel plus bevacizumab every 3 weeks and oral metronomic cyclophosphamide for 6 months. Trastuzumab was added for patients with HER2+ tumors and endocrine therapy was added for patients with estrogen receptor and/or progesterone receptor ≥ 10% tumors. Oral metronomic capecitabine and cyclophosphamide was continued for 6 months after surgery in those patients with a response. The primary efficacy endpoints were pathologic complete remission (pCR) and the objective response. Results: From July 2010 to December 2013, 34 patients with IBC were included. The surrogate intrinsic tumor subtypes were as follows: luminal B-like (HER2−), 10 (29%); luminal B-like (HER2+), 8 (24%); HER2+ (nonluminal), 6 (18%); and triple negative, 10 (29%). An objective response was obtained in 30 patients (88%; 95% confidence interval, 73%-97%) and a pCR in 10 patients (29%; 95% confidence interval, 15%-48%). The proportion of pCR was significantly greater in the patients with HER2+ tumors (57%) than in patients with triple-negative (20%) or luminal B-like (HER2−) tumors (0%; P =.019). After a median follow-up of 4.4 years, the 5-year disease-free survival and overall survival was 58% and 72%, respectively. The achievement of pCR was associated with longer disease-free (P =.12) and overall (P =.029) survival. Conclusion: In patients with IBC, neoadjuvant treatment with the investigated regimen was successful and well tolerated. Further studies evaluating the potential benefit of an antiangiogenic strategy in this setting are awaited.

KW - Antiangiogenesis

KW - IBC

KW - Metronomic chemotherapy

KW - Neoadjuvant chemotherapy

KW - Outcome

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U2 - 10.1016/j.clbc.2018.01.010

DO - 10.1016/j.clbc.2018.01.010

M3 - Article

AN - SCOPUS:85042459190

VL - 18

SP - 328

EP - 335

JO - Clinical Breast Cancer

JF - Clinical Breast Cancer

SN - 1526-8209

IS - 4

ER -