Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era

Filippo Montemurro, Stefania Redana, Giuseppe Viale, Giuseppina Sanna, Michela Donadio, Giorgio Valabrega, Barbara Del Curto, Alberto Bottini, Gerardo Botti, Angelo Paolo Dei Tos, Maria Elena Jacomuzzi, Maurizio Di Bonito, Saverio Danese, Matteo Clavarezza, J. Kulka, Silvana Di Palma, Antonio Durando, Anna Sapino, Massimo Aglietta

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy. Patients and Methods: From the clinical records of 407 patients with HER2-positive advanced breast cancer, we identified 279 patients progressing during an initial trastuzumab-based treatment. Of these patients, 83 continued trastuzumab in addition to chemotherapy, and 112 received chemotherapy alone. Results: We found no difference in response rate (28% vs. 30%; P = .5), median time to second tumor progression (8.4 months vs. 7 months; P = .24), or median postprogression survival (20.6 months and 15.4 months; P = .29) according to whether patients continued or stopped trastuzumab. At multivariate analysis, continuation of trastuzumab was associated with a statistically insignificant trend toward reduced risk of second progression (hazard ratio, 0.753; P = .08). Conclusion: Patients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy. For these patients, there is evidence from a large randomized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib.

Original languageEnglish
Pages (from-to)436-442
Number of pages7
JournalClinical Breast Cancer
Volume8
Issue number5
DOIs
Publication statusPublished - Oct 1 2008

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Breast Neoplasms
Drug Therapy
Therapeutics
Protein-Tyrosine Kinases
lapatinib
Trastuzumab
Epidermal Growth Factor Receptor
Disease Progression
Neoplasms
Multivariate Analysis
Monoclonal Antibodies
Survival

Keywords

  • Breast neoplasms
  • Disease progression
  • Drug resistance
  • Tyrosine kinase inhibition

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era. / Montemurro, Filippo; Redana, Stefania; Viale, Giuseppe; Sanna, Giuseppina; Donadio, Michela; Valabrega, Giorgio; Del Curto, Barbara; Bottini, Alberto; Botti, Gerardo; Paolo Dei Tos, Angelo; Jacomuzzi, Maria Elena; Di Bonito, Maurizio; Danese, Saverio; Clavarezza, Matteo; Kulka, J.; Di Palma, Silvana; Durando, Antonio; Sapino, Anna; Aglietta, Massimo.

In: Clinical Breast Cancer, Vol. 8, No. 5, 01.10.2008, p. 436-442.

Research output: Contribution to journalArticle

Montemurro, F, Redana, S, Viale, G, Sanna, G, Donadio, M, Valabrega, G, Del Curto, B, Bottini, A, Botti, G, Paolo Dei Tos, A, Jacomuzzi, ME, Di Bonito, M, Danese, S, Clavarezza, M, Kulka, J, Di Palma, S, Durando, A, Sapino, A & Aglietta, M 2008, 'Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era', Clinical Breast Cancer, vol. 8, no. 5, pp. 436-442. https://doi.org/10.3816/CBC.2008.n.053
Montemurro, Filippo ; Redana, Stefania ; Viale, Giuseppe ; Sanna, Giuseppina ; Donadio, Michela ; Valabrega, Giorgio ; Del Curto, Barbara ; Bottini, Alberto ; Botti, Gerardo ; Paolo Dei Tos, Angelo ; Jacomuzzi, Maria Elena ; Di Bonito, Maurizio ; Danese, Saverio ; Clavarezza, Matteo ; Kulka, J. ; Di Palma, Silvana ; Durando, Antonio ; Sapino, Anna ; Aglietta, Massimo. / Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era. In: Clinical Breast Cancer. 2008 ; Vol. 8, No. 5. pp. 436-442.
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abstract = "Background: Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy. Patients and Methods: From the clinical records of 407 patients with HER2-positive advanced breast cancer, we identified 279 patients progressing during an initial trastuzumab-based treatment. Of these patients, 83 continued trastuzumab in addition to chemotherapy, and 112 received chemotherapy alone. Results: We found no difference in response rate (28{\%} vs. 30{\%}; P = .5), median time to second tumor progression (8.4 months vs. 7 months; P = .24), or median postprogression survival (20.6 months and 15.4 months; P = .29) according to whether patients continued or stopped trastuzumab. At multivariate analysis, continuation of trastuzumab was associated with a statistically insignificant trend toward reduced risk of second progression (hazard ratio, 0.753; P = .08). Conclusion: Patients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy. For these patients, there is evidence from a large randomized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib.",
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T1 - Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era

AU - Montemurro, Filippo

AU - Redana, Stefania

AU - Viale, Giuseppe

AU - Sanna, Giuseppina

AU - Donadio, Michela

AU - Valabrega, Giorgio

AU - Del Curto, Barbara

AU - Bottini, Alberto

AU - Botti, Gerardo

AU - Paolo Dei Tos, Angelo

AU - Jacomuzzi, Maria Elena

AU - Di Bonito, Maurizio

AU - Danese, Saverio

AU - Clavarezza, Matteo

AU - Kulka, J.

AU - Di Palma, Silvana

AU - Durando, Antonio

AU - Sapino, Anna

AU - Aglietta, Massimo

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Background: Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy. Patients and Methods: From the clinical records of 407 patients with HER2-positive advanced breast cancer, we identified 279 patients progressing during an initial trastuzumab-based treatment. Of these patients, 83 continued trastuzumab in addition to chemotherapy, and 112 received chemotherapy alone. Results: We found no difference in response rate (28% vs. 30%; P = .5), median time to second tumor progression (8.4 months vs. 7 months; P = .24), or median postprogression survival (20.6 months and 15.4 months; P = .29) according to whether patients continued or stopped trastuzumab. At multivariate analysis, continuation of trastuzumab was associated with a statistically insignificant trend toward reduced risk of second progression (hazard ratio, 0.753; P = .08). Conclusion: Patients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy. For these patients, there is evidence from a large randomized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib.

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