Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer

Issam Makhoul, Vicki Klimberg, Soheila Korourian, Ronda S. Henry-Tillman, Eric R. Siegel, Kent C. Westbrook, Laura F. Hutchins

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: To evaluate the pathologic complete response (pCR) and safety of bevacizumab (B) with chemotherapy in the neoadjuvant setting of breast cancer (BC). Methods: A prospective single-arm, single-institution phase II trial for women with stage IIA-B/IIIA-B-C BC. Patients received neoadjuvant docetaxel, cyclophosphamide, B every 3 weeks for 4 cycles followed by doxorubicin every 3 weeks for 4 cycles followed by surgery. After healing, B was given every 3 weeks for 9 cycles. Radiation therapy, trastuzumab and endocrine therapy were given as indicated. Results: Thirty-nine of 40 patients were evaluable. Median age of participants was 45 years (range, 26 to 72 y). The most serious grade 3 adverse events were infection (4), congestive heart failure (2), and pulmonary embolism (1). Thirty-eight of 39 patients underwent surgery. The pCR rate was 41% (16/39), significantly higher than the null-hypothesis rate of 25% (P=0.0204). Rates of pCR were 52% (15/29) in ductal carcinoma compared with 10% (1/10) in nonductal disease (P=0.021), and 59% (10/17) in estrogen receptor-/progesteron receptor- patients compared with 27% (6/22) among patient with at least one positive hormone receptor (P=0.047). African Americans (AA) had 75% pCR (9/12), whereas Whites had only 28% pCR (7/25; P=0.0069), possibly in part because 100% of AA (12/12) had ductal carcinoma compared with only 64% (16/25) of Whites (P=0.017). Conclusions: Chemotherapy with B improved pCR in BC patients, but was associated with significant toxicity and rare but very serious complications. The improvement was more pronounced in AA patients, those with ductal carcinoma, and those with estrogen receptor-/progesteron receptor - BC.ClinicalTrials.gov Identifier: NCT00203502.

Original languageEnglish (US)
Pages (from-to)74-79
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume38
Issue number1
DOIs
StatePublished - Feb 2 2015
Externally publishedYes

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Hormones
Breast Neoplasms
Drug Therapy
Ductal Carcinoma
African Americans
docetaxel
Progesterone Receptors
Estrogen Receptors
Bevacizumab
Pulmonary Embolism
Doxorubicin
Cyclophosphamide
Radiotherapy
Heart Failure
Safety
Infection
Therapeutics

Keywords

  • antiangiogenic therapy
  • bevacizumab
  • Cancer
  • neoadjuvant chemotherapy
  • pathologic complete response

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer. / Makhoul, Issam; Klimberg, Vicki; Korourian, Soheila; Henry-Tillman, Ronda S.; Siegel, Eric R.; Westbrook, Kent C.; Hutchins, Laura F.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 38, No. 1, 02.02.2015, p. 74-79.

Research output: Contribution to journalArticle

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abstract = "Objectives: To evaluate the pathologic complete response (pCR) and safety of bevacizumab (B) with chemotherapy in the neoadjuvant setting of breast cancer (BC). Methods: A prospective single-arm, single-institution phase II trial for women with stage IIA-B/IIIA-B-C BC. Patients received neoadjuvant docetaxel, cyclophosphamide, B every 3 weeks for 4 cycles followed by doxorubicin every 3 weeks for 4 cycles followed by surgery. After healing, B was given every 3 weeks for 9 cycles. Radiation therapy, trastuzumab and endocrine therapy were given as indicated. Results: Thirty-nine of 40 patients were evaluable. Median age of participants was 45 years (range, 26 to 72 y). The most serious grade 3 adverse events were infection (4), congestive heart failure (2), and pulmonary embolism (1). Thirty-eight of 39 patients underwent surgery. The pCR rate was 41{\%} (16/39), significantly higher than the null-hypothesis rate of 25{\%} (P=0.0204). Rates of pCR were 52{\%} (15/29) in ductal carcinoma compared with 10{\%} (1/10) in nonductal disease (P=0.021), and 59{\%} (10/17) in estrogen receptor-/progesteron receptor- patients compared with 27{\%} (6/22) among patient with at least one positive hormone receptor (P=0.047). African Americans (AA) had 75{\%} pCR (9/12), whereas Whites had only 28{\%} pCR (7/25; P=0.0069), possibly in part because 100{\%} of AA (12/12) had ductal carcinoma compared with only 64{\%} (16/25) of Whites (P=0.017). Conclusions: Chemotherapy with B improved pCR in BC patients, but was associated with significant toxicity and rare but very serious complications. The improvement was more pronounced in AA patients, those with ductal carcinoma, and those with estrogen receptor-/progesteron receptor - BC.ClinicalTrials.gov Identifier: NCT00203502.",
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T1 - Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer

AU - Makhoul, Issam

AU - Klimberg, Vicki

AU - Korourian, Soheila

AU - Henry-Tillman, Ronda S.

AU - Siegel, Eric R.

AU - Westbrook, Kent C.

AU - Hutchins, Laura F.

PY - 2015/2/2

Y1 - 2015/2/2

N2 - Objectives: To evaluate the pathologic complete response (pCR) and safety of bevacizumab (B) with chemotherapy in the neoadjuvant setting of breast cancer (BC). Methods: A prospective single-arm, single-institution phase II trial for women with stage IIA-B/IIIA-B-C BC. Patients received neoadjuvant docetaxel, cyclophosphamide, B every 3 weeks for 4 cycles followed by doxorubicin every 3 weeks for 4 cycles followed by surgery. After healing, B was given every 3 weeks for 9 cycles. Radiation therapy, trastuzumab and endocrine therapy were given as indicated. Results: Thirty-nine of 40 patients were evaluable. Median age of participants was 45 years (range, 26 to 72 y). The most serious grade 3 adverse events were infection (4), congestive heart failure (2), and pulmonary embolism (1). Thirty-eight of 39 patients underwent surgery. The pCR rate was 41% (16/39), significantly higher than the null-hypothesis rate of 25% (P=0.0204). Rates of pCR were 52% (15/29) in ductal carcinoma compared with 10% (1/10) in nonductal disease (P=0.021), and 59% (10/17) in estrogen receptor-/progesteron receptor- patients compared with 27% (6/22) among patient with at least one positive hormone receptor (P=0.047). African Americans (AA) had 75% pCR (9/12), whereas Whites had only 28% pCR (7/25; P=0.0069), possibly in part because 100% of AA (12/12) had ductal carcinoma compared with only 64% (16/25) of Whites (P=0.017). Conclusions: Chemotherapy with B improved pCR in BC patients, but was associated with significant toxicity and rare but very serious complications. The improvement was more pronounced in AA patients, those with ductal carcinoma, and those with estrogen receptor-/progesteron receptor - BC.ClinicalTrials.gov Identifier: NCT00203502.

AB - Objectives: To evaluate the pathologic complete response (pCR) and safety of bevacizumab (B) with chemotherapy in the neoadjuvant setting of breast cancer (BC). Methods: A prospective single-arm, single-institution phase II trial for women with stage IIA-B/IIIA-B-C BC. Patients received neoadjuvant docetaxel, cyclophosphamide, B every 3 weeks for 4 cycles followed by doxorubicin every 3 weeks for 4 cycles followed by surgery. After healing, B was given every 3 weeks for 9 cycles. Radiation therapy, trastuzumab and endocrine therapy were given as indicated. Results: Thirty-nine of 40 patients were evaluable. Median age of participants was 45 years (range, 26 to 72 y). The most serious grade 3 adverse events were infection (4), congestive heart failure (2), and pulmonary embolism (1). Thirty-eight of 39 patients underwent surgery. The pCR rate was 41% (16/39), significantly higher than the null-hypothesis rate of 25% (P=0.0204). Rates of pCR were 52% (15/29) in ductal carcinoma compared with 10% (1/10) in nonductal disease (P=0.021), and 59% (10/17) in estrogen receptor-/progesteron receptor- patients compared with 27% (6/22) among patient with at least one positive hormone receptor (P=0.047). African Americans (AA) had 75% pCR (9/12), whereas Whites had only 28% pCR (7/25; P=0.0069), possibly in part because 100% of AA (12/12) had ductal carcinoma compared with only 64% (16/25) of Whites (P=0.017). Conclusions: Chemotherapy with B improved pCR in BC patients, but was associated with significant toxicity and rare but very serious complications. The improvement was more pronounced in AA patients, those with ductal carcinoma, and those with estrogen receptor-/progesteron receptor - BC.ClinicalTrials.gov Identifier: NCT00203502.

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