Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2–positive breast cancer: Three-year outcomes from the phase III KristinE study

Sara A. Hurvitz, Miguel Martin, Kyung Hae Jung, Chiun Sheng Huang, Nadia Harbeck, Vicente Valero, Daniil Stroyakovskiy, Hans Wildiers, Mario Campone, Jean François Boileau, Peter A. Fasching, Karen Afenjar, Gonzalo Spera, Vanesa Lopez-Valverde, Chunyan Song, Peter Trask, Thomas Boulet, Joseph A. Sparano, W. Fraser Symmans, Alastair M. ThompsonDennis Slamon

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Abstract

PURPOSE The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2–positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE. METHODS Patients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery). RESULTS Of patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment. CONCLUSION Compared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment.

Original languageEnglish (US)
Pages (from-to)2206-2216
Number of pages11
JournalJournal of Clinical Oncology
Volume37
Issue number25
DOIs
StatePublished - Sep 1 2019

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Epidermal Growth Factor Receptor
Breast Neoplasms
Disease-Free Survival
Neoadjuvant Therapy
docetaxel
Therapeutics
Carboplatin
pertuzumab
ado-trastuzumab emtansine
Survival
Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2–positive breast cancer : Three-year outcomes from the phase III KristinE study. / Hurvitz, Sara A.; Martin, Miguel; Jung, Kyung Hae; Huang, Chiun Sheng; Harbeck, Nadia; Valero, Vicente; Stroyakovskiy, Daniil; Wildiers, Hans; Campone, Mario; Boileau, Jean François; Fasching, Peter A.; Afenjar, Karen; Spera, Gonzalo; Lopez-Valverde, Vanesa; Song, Chunyan; Trask, Peter; Boulet, Thomas; Sparano, Joseph A.; Fraser Symmans, W.; Thompson, Alastair M.; Slamon, Dennis.

In: Journal of Clinical Oncology, Vol. 37, No. 25, 01.09.2019, p. 2206-2216.

Research output: Contribution to journalArticle

Hurvitz, SA, Martin, M, Jung, KH, Huang, CS, Harbeck, N, Valero, V, Stroyakovskiy, D, Wildiers, H, Campone, M, Boileau, JF, Fasching, PA, Afenjar, K, Spera, G, Lopez-Valverde, V, Song, C, Trask, P, Boulet, T, Sparano, JA, Fraser Symmans, W, Thompson, AM & Slamon, D 2019, 'Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2–positive breast cancer: Three-year outcomes from the phase III KristinE study', Journal of Clinical Oncology, vol. 37, no. 25, pp. 2206-2216. https://doi.org/10.1200/JCO.19.00882
Hurvitz, Sara A. ; Martin, Miguel ; Jung, Kyung Hae ; Huang, Chiun Sheng ; Harbeck, Nadia ; Valero, Vicente ; Stroyakovskiy, Daniil ; Wildiers, Hans ; Campone, Mario ; Boileau, Jean François ; Fasching, Peter A. ; Afenjar, Karen ; Spera, Gonzalo ; Lopez-Valverde, Vanesa ; Song, Chunyan ; Trask, Peter ; Boulet, Thomas ; Sparano, Joseph A. ; Fraser Symmans, W. ; Thompson, Alastair M. ; Slamon, Dennis. / Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2–positive breast cancer : Three-year outcomes from the phase III KristinE study. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 25. pp. 2206-2216.
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title = "Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2–positive breast cancer: Three-year outcomes from the phase III KristinE study",
abstract = "PURPOSE The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2–positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4{\%} v 55.7{\%}; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE. METHODS Patients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery). RESULTS Of patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95{\%} CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7{\%}] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95{\%} CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95{\%} CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8{\%} v 67.7{\%}) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5{\%} v 9.9{\%}) and AEs leading to treatment discontinuation (18.4{\%} v 3.8{\%}) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment. CONCLUSION Compared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment.",
author = "Hurvitz, {Sara A.} and Miguel Martin and Jung, {Kyung Hae} and Huang, {Chiun Sheng} and Nadia Harbeck and Vicente Valero and Daniil Stroyakovskiy and Hans Wildiers and Mario Campone and Boileau, {Jean Fran{\cc}ois} and Fasching, {Peter A.} and Karen Afenjar and Gonzalo Spera and Vanesa Lopez-Valverde and Chunyan Song and Peter Trask and Thomas Boulet and Sparano, {Joseph A.} and {Fraser Symmans}, W. and Thompson, {Alastair M.} and Dennis Slamon",
year = "2019",
month = "9",
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doi = "10.1200/JCO.19.00882",
language = "English (US)",
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pages = "2206--2216",
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TY - JOUR

T1 - Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2–positive breast cancer

T2 - Three-year outcomes from the phase III KristinE study

AU - Hurvitz, Sara A.

AU - Martin, Miguel

AU - Jung, Kyung Hae

AU - Huang, Chiun Sheng

AU - Harbeck, Nadia

AU - Valero, Vicente

AU - Stroyakovskiy, Daniil

AU - Wildiers, Hans

AU - Campone, Mario

AU - Boileau, Jean François

AU - Fasching, Peter A.

AU - Afenjar, Karen

AU - Spera, Gonzalo

AU - Lopez-Valverde, Vanesa

AU - Song, Chunyan

AU - Trask, Peter

AU - Boulet, Thomas

AU - Sparano, Joseph A.

AU - Fraser Symmans, W.

AU - Thompson, Alastair M.

AU - Slamon, Dennis

PY - 2019/9/1

Y1 - 2019/9/1

N2 - PURPOSE The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2–positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE. METHODS Patients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery). RESULTS Of patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment. CONCLUSION Compared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment.

AB - PURPOSE The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2–positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE. METHODS Patients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery). RESULTS Of patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment. CONCLUSION Compared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment.

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