Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial A Randomized Phase 3 Clinical Trial

Luca Gianni, Mauro Mansutti, Antonio Anton, Lourdes Calvo, Giancarlo Bisagni, Begona Bermejo, Vladimir Semiglazov, Marc Thill, Jose Ignacio Chacon, Arlene Chan, Serafin Morales, Isabel Alvarez, Arrate Plazaola, Milvia Zambetti, Andrew D. Redfern, Christian Dittrich, Rebecca Alexandra Dent, Domenico Magazzu, Raffaella De Fato, Pinuccia Valagussa & 1 others Ignacio Tusquets

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

IMPORTANCE Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial.

OBJECTIVE To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting.

DESIGN, SETTING, AND PARTICIPANTS In this multicenter, open-label study, in collaboration with Grupo Espanol de Investigacion en Cancer de Mama (GEICAM) and Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90mg/m(2) (349 patients), or nab-paclitaxel, 125mg/m(2) (346 patients). The 2 drugs were given on weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice.

MAIN OUTCOMES AND MEASURES The primary end pointwas the rate of pCR, defined as absence of invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end point was to assess tolerability and safety of the 2 regimens. RESULTS From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not statistically significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77; 95% CI, 0.52-1.13; P =.19). Overall, 38 of 335 patients (11.3%) 11.3% of patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337 patient (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6 of 335 patients (1.8%) and in 15 of 337 (4.5%), respectively.

CONCLUSIONS AND RELEVANCE The improved rate of pCR after nab-paclitaxel was not statistically significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the most significant factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome.

Original languageEnglish
Pages (from-to)302-308
Number of pages7
JournalJAMA Oncology
Volume4
Issue number3
DOIs
Publication statusPublished - Mar 2018
Externally publishedYes

Cite this

Gianni, Luca ; Mansutti, Mauro ; Anton, Antonio ; Calvo, Lourdes ; Bisagni, Giancarlo ; Bermejo, Begona ; Semiglazov, Vladimir ; Thill, Marc ; Ignacio Chacon, Jose ; Chan, Arlene ; Morales, Serafin ; Alvarez, Isabel ; Plazaola, Arrate ; Zambetti, Milvia ; Redfern, Andrew D. ; Dittrich, Christian ; Dent, Rebecca Alexandra ; Magazzu, Domenico ; De Fato, Raffaella ; Valagussa, Pinuccia ; Tusquets, Ignacio. / Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial A Randomized Phase 3 Clinical Trial. In: JAMA Oncology. 2018 ; Vol. 4, No. 3. pp. 302-308.
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title = "Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial A Randomized Phase 3 Clinical Trial",
abstract = "IMPORTANCE Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial.OBJECTIVE To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting.DESIGN, SETTING, AND PARTICIPANTS In this multicenter, open-label study, in collaboration with Grupo Espanol de Investigacion en Cancer de Mama (GEICAM) and Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90mg/m(2) (349 patients), or nab-paclitaxel, 125mg/m(2) (346 patients). The 2 drugs were given on weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice.MAIN OUTCOMES AND MEASURES The primary end pointwas the rate of pCR, defined as absence of invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end point was to assess tolerability and safety of the 2 regimens. RESULTS From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5{\%}) was not statistically significant compared with paclitaxel (18.6{\%}; odds ratio [OR], 0.77; 95{\%} CI, 0.52-1.13; P =.19). Overall, 38 of 335 patients (11.3{\%}) 11.3{\%} of patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337 patient (16.0{\%}) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6 of 335 patients (1.8{\%}) and in 15 of 337 (4.5{\%}), respectively.CONCLUSIONS AND RELEVANCE The improved rate of pCR after nab-paclitaxel was not statistically significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the most significant factor (OR, 4.85; 95{\%} CI, 3.28-7.18) influencing treatment outcome.",
keywords = "SOLVENT-BASED PACLITAXEL, III TRIAL, CHEMOTHERAPY, CYCLOPHOSPHAMIDE",
author = "Luca Gianni and Mauro Mansutti and Antonio Anton and Lourdes Calvo and Giancarlo Bisagni and Begona Bermejo and Vladimir Semiglazov and Marc Thill and {Ignacio Chacon}, Jose and Arlene Chan and Serafin Morales and Isabel Alvarez and Arrate Plazaola and Milvia Zambetti and Redfern, {Andrew D.} and Christian Dittrich and Dent, {Rebecca Alexandra} and Domenico Magazzu and {De Fato}, Raffaella and Pinuccia Valagussa and Ignacio Tusquets",
year = "2018",
month = "3",
doi = "10.1001/jamaoncol.2017.4612",
language = "English",
volume = "4",
pages = "302--308",
journal = "JAMA Oncology",
issn = "2374-2437",
publisher = "American Medical Association",
number = "3",

}

Gianni, L, Mansutti, M, Anton, A, Calvo, L, Bisagni, G, Bermejo, B, Semiglazov, V, Thill, M, Ignacio Chacon, J, Chan, A, Morales, S, Alvarez, I, Plazaola, A, Zambetti, M, Redfern, AD, Dittrich, C, Dent, RA, Magazzu, D, De Fato, R, Valagussa, P & Tusquets, I 2018, 'Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial A Randomized Phase 3 Clinical Trial' JAMA Oncology, vol. 4, no. 3, pp. 302-308. https://doi.org/10.1001/jamaoncol.2017.4612

Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial A Randomized Phase 3 Clinical Trial. / Gianni, Luca; Mansutti, Mauro; Anton, Antonio; Calvo, Lourdes; Bisagni, Giancarlo; Bermejo, Begona; Semiglazov, Vladimir; Thill, Marc; Ignacio Chacon, Jose; Chan, Arlene; Morales, Serafin; Alvarez, Isabel; Plazaola, Arrate; Zambetti, Milvia; Redfern, Andrew D.; Dittrich, Christian; Dent, Rebecca Alexandra; Magazzu, Domenico; De Fato, Raffaella; Valagussa, Pinuccia; Tusquets, Ignacio.

In: JAMA Oncology, Vol. 4, No. 3, 03.2018, p. 302-308.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial A Randomized Phase 3 Clinical Trial

AU - Gianni, Luca

AU - Mansutti, Mauro

AU - Anton, Antonio

AU - Calvo, Lourdes

AU - Bisagni, Giancarlo

AU - Bermejo, Begona

AU - Semiglazov, Vladimir

AU - Thill, Marc

AU - Ignacio Chacon, Jose

AU - Chan, Arlene

AU - Morales, Serafin

AU - Alvarez, Isabel

AU - Plazaola, Arrate

AU - Zambetti, Milvia

AU - Redfern, Andrew D.

AU - Dittrich, Christian

AU - Dent, Rebecca Alexandra

AU - Magazzu, Domenico

AU - De Fato, Raffaella

AU - Valagussa, Pinuccia

AU - Tusquets, Ignacio

PY - 2018/3

Y1 - 2018/3

N2 - IMPORTANCE Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial.OBJECTIVE To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting.DESIGN, SETTING, AND PARTICIPANTS In this multicenter, open-label study, in collaboration with Grupo Espanol de Investigacion en Cancer de Mama (GEICAM) and Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90mg/m(2) (349 patients), or nab-paclitaxel, 125mg/m(2) (346 patients). The 2 drugs were given on weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice.MAIN OUTCOMES AND MEASURES The primary end pointwas the rate of pCR, defined as absence of invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end point was to assess tolerability and safety of the 2 regimens. RESULTS From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not statistically significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77; 95% CI, 0.52-1.13; P =.19). Overall, 38 of 335 patients (11.3%) 11.3% of patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337 patient (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6 of 335 patients (1.8%) and in 15 of 337 (4.5%), respectively.CONCLUSIONS AND RELEVANCE The improved rate of pCR after nab-paclitaxel was not statistically significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the most significant factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome.

AB - IMPORTANCE Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial.OBJECTIVE To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting.DESIGN, SETTING, AND PARTICIPANTS In this multicenter, open-label study, in collaboration with Grupo Espanol de Investigacion en Cancer de Mama (GEICAM) and Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90mg/m(2) (349 patients), or nab-paclitaxel, 125mg/m(2) (346 patients). The 2 drugs were given on weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice.MAIN OUTCOMES AND MEASURES The primary end pointwas the rate of pCR, defined as absence of invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end point was to assess tolerability and safety of the 2 regimens. RESULTS From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not statistically significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77; 95% CI, 0.52-1.13; P =.19). Overall, 38 of 335 patients (11.3%) 11.3% of patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337 patient (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6 of 335 patients (1.8%) and in 15 of 337 (4.5%), respectively.CONCLUSIONS AND RELEVANCE The improved rate of pCR after nab-paclitaxel was not statistically significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the most significant factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome.

KW - SOLVENT-BASED PACLITAXEL

KW - III TRIAL

KW - CHEMOTHERAPY

KW - CYCLOPHOSPHAMIDE

U2 - 10.1001/jamaoncol.2017.4612

DO - 10.1001/jamaoncol.2017.4612

M3 - Article

VL - 4

SP - 302

EP - 308

JO - JAMA Oncology

JF - JAMA Oncology

SN - 2374-2437

IS - 3

ER -