PMID- 31157583
OWN - NLM
STAT- MEDLINE
DCOM- 20200610
LR  - 20200610
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 37
IP  - 25
DP  - 2019 Sep 1
TI  - Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor 
      Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III 
      KRISTINE Study.
PG  - 2206-2216
LID - 10.1200/JCO.19.00882 [doi]
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.
FAU - Hurvitz, Sara A
AU  - Hurvitz SA
AD  - University of California, Los Angeles, Los Angeles, CA.
FAU - Martin, Miguel
AU  - Martin M
AD  - Universidad Complutense, CUBERONC, GEICAM, Madrid, Spain.
FAU - Jung, Kyung Hae
AU  - Jung KH
AD  - Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
FAU - Huang, Chiun-Sheng
AU  - Huang CS
AD  - National Taiwan University Hospital, National Taiwan University College of 
      Medicine, Taipei, Republic of China.
FAU - Harbeck, Nadia
AU  - Harbeck N
AD  - University of Munich, Munich, Germany.
FAU - Valero, Vicente
AU  - Valero V
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX.
FAU - Stroyakovskiy, Daniil
AU  - Stroyakovskiy D
AD  - Moscow City Oncology Hospital 62, Moscow, Russia.
FAU - Wildiers, Hans
AU  - Wildiers H
AD  - University Hospitals Leuven, Leuven, Belgium.
FAU - Campone, Mario
AU  - Campone M
AD  - Centre Rene Gauducheau, Saint-Herblain, France.
FAU - Boileau, Jean-Francois
AU  - Boileau JF
AD  - McGill University, Jewish General Hospital Segal Cancer Centre, Montreal, Quebec, 
      Canada.
FAU - Fasching, Peter A
AU  - Fasching PA
AD  - University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 
      Erlangen, Germany.
FAU - Afenjar, Karen
AU  - Afenjar K
AD  - Translational Research in Oncology, Paris, France.
FAU - Spera, Gonzalo
AU  - Spera G
AD  - Translational Research in Oncology, Montevideo, Uruguay.
FAU - Lopez-Valverde, Vanesa
AU  - Lopez-Valverde V
AD  - PAREXEL International GmbH, Berlin, Germany.
FAU - Song, Chunyan
AU  - Song C
AD  - Genentech, South San Francisco, CA.
FAU - Trask, Peter
AU  - Trask P
AD  - Genentech, South San Francisco, CA.
FAU - Boulet, Thomas
AU  - Boulet T
AD  - PAREXEL International GmbH, Berlin, Germany.
FAU - Sparano, Joseph A
AU  - Sparano JA
AD  - Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
FAU - Symmans, W Fraser
AU  - Symmans WF
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX.
FAU - Thompson, Alastair M
AU  - Thompson AM
AD  - Baylor College of Medicine, Houston, TX.
FAU - Slamon, Dennis
AU  - Slamon D
AD  - University of California, Los Angeles, Los Angeles, CA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02131064
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190603
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 15H5577CQD (Docetaxel)
RN  - BG3F62OND5 (Carboplatin)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - K16AIQ8CTM (pertuzumab)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
CIN - J Clin Oncol. 2019 Sep 1;37(25):2189-2192. PMID: 31157582
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/*enzymology
MH  - Carboplatin/administration & dosage
MH  - Chemotherapy, Adjuvant
MH  - Disease-Free Survival
MH  - Docetaxel/administration & dosage
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Middle Aged
MH  - Neoadjuvant Therapy
MH  - Receptor, ErbB-2/*metabolism
MH  - Trastuzumab/administration & dosage
PMC - PMC6774816
EDAT- 2019/06/04 06:00
MHDA- 2020/06/11 06:00
PMCR- 2019/06/03
CRDT- 2019/06/04 06:00
PHST- 2019/06/04 06:00 [pubmed]
PHST- 2020/06/11 06:00 [medline]
PHST- 2019/06/04 06:00 [entrez]
PHST- 2019/06/03 00:00 [pmc-release]
AID - 1900882 [pii]
AID - 10.1200/JCO.19.00882 [doi]
PST - ppublish
SO  - J Clin Oncol. 2019 Sep 1;37(25):2206-2216. doi: 10.1200/JCO.19.00882. Epub 2019 
      Jun 3.