Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: Results of the randomized phase II CHER-LOB study

Valentina Guarneri, Antonio Frassoldati, Alberto Bottini, Katia Cagossi, Giancarlo Bisagni, Samanta Sarti, Alberto Ravaioli, Luigi Cavanna, Giovanni Giardina, Antonino Musolino, Michael Untch, Laura Orlando, Fabrizio Artioli, Corrado Boni, Daniele Giulio Generali, Patrizia Serra, Michela Bagnalasta, Luca Marini, Federico Piacentini, Roberto D'AmicoPierFranco Conte

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Abstract

Purpose: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes). Patients and Methods: In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m2) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily. Results: A total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B and C, respectively. The pCR rates were 25% (90% CI, 13.1% to 36.9%) in arm A, 26.3% (90% CI, 14.5% to 38.1%) in arm B, and 46.7% (90% CI, 34.4% to 58.9%) in arm C (exploratory P = .019). Conclusion: The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.

Original languageEnglish
Pages (from-to)1989-1995
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number16
DOIs
Publication statusPublished - Jun 1 2012

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Breast Neoplasms
Drug Therapy
Epirubicin
Segmental Mastectomy
Anthracyclines
Paclitaxel
human ERBB2 protein
lapatinib
Trastuzumab
Fluorouracil
Cyclophosphamide
Diarrhea
Heart Failure
Liver
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer : Results of the randomized phase II CHER-LOB study. / Guarneri, Valentina; Frassoldati, Antonio; Bottini, Alberto; Cagossi, Katia; Bisagni, Giancarlo; Sarti, Samanta; Ravaioli, Alberto; Cavanna, Luigi; Giardina, Giovanni; Musolino, Antonino; Untch, Michael; Orlando, Laura; Artioli, Fabrizio; Boni, Corrado; Generali, Daniele Giulio; Serra, Patrizia; Bagnalasta, Michela; Marini, Luca; Piacentini, Federico; D'Amico, Roberto; Conte, PierFranco.

In: Journal of Clinical Oncology, Vol. 30, No. 16, 01.06.2012, p. 1989-1995.

Research output: Contribution to journalArticle

Guarneri, V, Frassoldati, A, Bottini, A, Cagossi, K, Bisagni, G, Sarti, S, Ravaioli, A, Cavanna, L, Giardina, G, Musolino, A, Untch, M, Orlando, L, Artioli, F, Boni, C, Generali, DG, Serra, P, Bagnalasta, M, Marini, L, Piacentini, F, D'Amico, R & Conte, P 2012, 'Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: Results of the randomized phase II CHER-LOB study', Journal of Clinical Oncology, vol. 30, no. 16, pp. 1989-1995. https://doi.org/10.1200/JCO.2011.39.0823
Guarneri, Valentina ; Frassoldati, Antonio ; Bottini, Alberto ; Cagossi, Katia ; Bisagni, Giancarlo ; Sarti, Samanta ; Ravaioli, Alberto ; Cavanna, Luigi ; Giardina, Giovanni ; Musolino, Antonino ; Untch, Michael ; Orlando, Laura ; Artioli, Fabrizio ; Boni, Corrado ; Generali, Daniele Giulio ; Serra, Patrizia ; Bagnalasta, Michela ; Marini, Luca ; Piacentini, Federico ; D'Amico, Roberto ; Conte, PierFranco. / Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer : Results of the randomized phase II CHER-LOB study. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 16. pp. 1989-1995.
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abstract = "Purpose: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes). Patients and Methods: In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m2) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily. Results: A total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7{\%}, 57.9{\%}, and 68.9{\%} in arms A, B and C, respectively. The pCR rates were 25{\%} (90{\%} CI, 13.1{\%} to 36.9{\%}) in arm A, 26.3{\%} (90{\%} CI, 14.5{\%} to 38.1{\%}) in arm B, and 46.7{\%} (90{\%} CI, 34.4{\%} to 58.9{\%}) in arm C (exploratory P = .019). Conclusion: The primary end point of the study was met, with a relative increase of 80{\%} in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.",
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T1 - Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer

T2 - Results of the randomized phase II CHER-LOB study

AU - Guarneri, Valentina

AU - Frassoldati, Antonio

AU - Bottini, Alberto

AU - Cagossi, Katia

AU - Bisagni, Giancarlo

AU - Sarti, Samanta

AU - Ravaioli, Alberto

AU - Cavanna, Luigi

AU - Giardina, Giovanni

AU - Musolino, Antonino

AU - Untch, Michael

AU - Orlando, Laura

AU - Artioli, Fabrizio

AU - Boni, Corrado

AU - Generali, Daniele Giulio

AU - Serra, Patrizia

AU - Bagnalasta, Michela

AU - Marini, Luca

AU - Piacentini, Federico

AU - D'Amico, Roberto

AU - Conte, PierFranco

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Purpose: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes). Patients and Methods: In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m2) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily. Results: A total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B and C, respectively. The pCR rates were 25% (90% CI, 13.1% to 36.9%) in arm A, 26.3% (90% CI, 14.5% to 38.1%) in arm B, and 46.7% (90% CI, 34.4% to 58.9%) in arm C (exploratory P = .019). Conclusion: The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.

AB - Purpose: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes). Patients and Methods: In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m2) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily. Results: A total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B and C, respectively. The pCR rates were 25% (90% CI, 13.1% to 36.9%) in arm A, 26.3% (90% CI, 14.5% to 38.1%) in arm B, and 46.7% (90% CI, 34.4% to 58.9%) in arm C (exploratory P = .019). Conclusion: The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.

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