A Study Evaluating Trastuzumab Emtansine Plus Pertuzumab Compared With Chemotherapy Plus Trastuzumab and Pertuzumab for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

A Randomized, Multicenter, Open-Label, Two-Arm, Phase III Neoadjuvant Study Evaluating Trastuzumab Emtansine Plus Pertuzumab Compared With Chemotherapy Plus Trastuzumab and Pertuzumab for Patients With HER2-Positive Breast Cancer

This is a randomized, multicenter, open-label, two-arm study in treatment-naive participants with operable, locally advanced, or inflammatory, centrally-assessed HER2-positive early breast cancer (EBC) whose primary tumors were greater than or equal to (>/=) 2 centimeters (cm). The study was designed to evaluate the efficacy and safety of trastuzumab emtansine + pertuzumab (experimental arm; T-DM1 + P) versus chemotherapy, trastuzumab + pertuzumab (control arm; TCH + P). The study comprised a neoadjuvant treatment period, followed by surgery, and an adjuvant treatment period.

Treatment can be stopped due to disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Carboplatin; Drug: Docetaxel; Drug: Pertuzumab; Drug: Trastuzumab; Drug: Trastuzumab Emtansine

• Study Type: Interventional
• Enrollment (Actual): 444
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Liège, Belgium, 4000
    • Clinique Saint-Joseph
  • Namur, Belgium, 5000
    • Clinique Ste-Elisabeth, Pharmacie
  • Wilrijk, Belgium, 2610
    • Sint Augustinus Wilrijk
• Canada
  • Quebec, Canada, G1S 4L8
    • CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ; Dept of Medical Oncology
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
    • Montreal, Quebec, Canada, H2L 4M1
      • Chum Hospital Notre Dame
• France
  • Angers, France, 49000
    • ICO - Paul Papin
  • Besancon, France, 25030
    • HOPITAL JEAN MINJOZ; Oncologie
  • Brest, France, 29200
    • Hopital Morvan
  • La Roche Sur Yon, France, 85925
    • CHD Les Oudairies
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Nantes, France, 44202
    • Centre Catherine de Sienne
  • Saint Herblain, France, 44805
    • Centre René Gauducheau
  • Strasbourg, France, 67091
    • Nouvel Hopital Civil - CHU Strasbourg
• Germany
  • Böblingen, Germany, 71032
    • Klinikum Sindelfingen-Böblingen; Frauenklinik
  • Düsseldorf, Germany, 40235
    • Luisenkrankenhaus GmbH, Brustzentrum
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen; Frauenklinik
  • Mainz, Germany, 55131
    • Universitätsklinikum Mainz
  • München, Germany, 80336
    • Interdisziplinares Onkologisches Zentrum
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 10408
    • National Cancer Center
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - Oncology
• Russian Federation
  • Kislino, Kursk Region, Russian Federation, 305524
    • Regional Oncology Hospital Of Kursk; Chemotherapy
  • Moscow, Russian Federation, 115478
    • S.I. Russian Oncological Research Center n.a. N.N. Blokhin
  • Orenburg, Russian Federation, 460021
    • State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis
  • Saratov, Russian Federation, 410004
    • Railway Clinical Hospital on Saratov - 2 Station Oao "Rzhd"
  • St Petersburg, Russian Federation, 197022
    • Saint-Petersburg City Clinical Oncology Dispensary
  • Moskovskaja Oblast
    • Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation, 143423
      • Moscow City Oncology Hospital #62
• Spain
  • Avila, Spain, 05071
    • Hospital Nuestra Señora de Sonsoles; servicio de Oncologia
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Oncologia
  • Barcelona, Spain, 08006
    • Fundacio Santa Creu I Sant Pau
  • Jaen, Spain, 23007
    • Complejo Hospitalario de Jaén
  • La Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
  • Madrid, Spain, 28223
    • Hospital Quiron de Madrid; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet; Servicio Oncologia
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
  • Guipuzcoa
    • San Sebastian, Guipuzcoa, Spain, 20014
      • IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia
  • Lerida
    • Lleida, Lerida, Spain, 25198
      • Hospital Universitari de Lleida Arnau de Vilanova
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery
  • Taipei, Taiwan, 11490
    • Tri-Service General Hospital
  • Taipei, Taiwan, 104
    • Mackay Memorial Hospital; Dept of Surgery
  • Taipei, Taiwan, 112
    • Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
  • Taipei City, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taipei City, Taiwan, 10041
    • National Taiwan Uni Hospital
• Ukraine
  • Cherkassy, Ukraine, 18009
    • Cherkassy Regional Oncological Hospital
  • Dnipropetrovsk, Ukraine, 43102
    • State Medical Academy; Oncology
  • Kharkiv, Ukraine, 61070
    • Karkiv Regional Oncology Center
  • Lvov, Ukraine, 79031
    • Lvov State Regional Center
• United States
  • California
    • Fullerton, California, United States, 92835
      • St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr
    • Los Angeles, California, United States, 90095-1772
      • Cancer Care Assoc Med Group
    • San Luis Obispo, California, United States, 93401
      • Coastal Integrative Cancer Care
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center Orlando
  • Maine
    • Scarborough, Maine, United States, 04074
      • New England Cancer Specialists
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada - Henderson
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Lake Success, New York, United States, 11042
      • ProHEALTH Care Associates LLP
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Hope A Women's Cancer Center
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Roper Bon Secours St. Francis Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed invasive breast cancer with a primary tumor size of greater than (>) 2 cm
• HER2-positive breast cancer
• Participants with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided all discrete lesions are sampled and centrally confirmed as HER2 positive
• Stage at presentation: cT2-cT4, cN0-cN3, cM0, according to American Joint Committee on Cancer (AJCC) staging system
• Known hormone receptor status of the primary tumor
• Participant agreement to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Baseline Left Ventricular Ejection Fraction (LVEF) >/= 55 percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA)
• Effective contraception as defined by protocol

Exclusion Criteria:

• Stage IV (metastatic) breast cancer
• Participants who have received prior anti-cancer therapy for breast cancer except those participants with a history of breast lobular carcinoma in situ (LCIS) that was surgically managed or ductal carcinoma in situ (DCIS) treated exclusively with mastectomy. In case of prior history of LCIS/DCIS, >5 years must have passed from surgery until diagnosis of current breast cancer
• Participants with multicentric (multiple tumors involving more than 1 quadrant) or bilateral breast cancer
• Participants who have undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
• Axillary lymph node dissection or positive sentinel lymph node prior to start of neoadjuvant therapy
• History of concurrent or previously non-breast malignancies except for appropriately treated (1) non-melanoma skin cancer and (2) in situ carcinomas, including cervix, colon, and skin. A participant with previous invasive non-breast cancer is eligible provided he/she has been disease-free >/= 5 years
• Treatment with any investigational drug within 28 days prior to randomization
• Current National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0
• Any significant concurrent medical or surgical conditions or findings that would jeopardize the participant's safety or ability to complete the study
• Current pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Trastuzumab (TCH) + Pertuzumab; Participants will receive pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion followed by trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion followed by docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).	Drug: Carboplatin; Carboplatin IV infusion at a dose to achieve an AUC of 6 mg*min/mL q3w; Drug: Docetaxel; Docetaxel 75 mg/m^2 IV infusion q3w; Drug: Pertuzumab; Pertuzumab 840 mg (loading dose); and 420 mg (maintenance dose) IV infusion q3w; Other Names: Perjeta®, RO4368451; Drug: Trastuzumab; Trastuzumab 8 mg/kg (loading dose); and 6 mg/kg (maintenance dose) IV infusion q3w; Other Names: Herceptin®
Experimental: Trastuzumab Emtansine (T-DM1) + Pertuzumab; Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).	Drug: Pertuzumab; Pertuzumab 840 mg (loading dose); and 420 mg (maintenance dose) IV infusion q3w; Other Names: Perjeta®, RO4368451; Drug: Trastuzumab Emtansine; Trastuzumab Emtansine 3.6 mg/kg IV infusion q3w; Other Names: Kadcyla®, RO5304020

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples	tpCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( that is [i.e.], ypT0/is, ypN0 in the American Joint Committee on Cancer [AJCC] staging system, 7th edition). Percentage of participants with tpCR was reported.	Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. 3 years OS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment.	From randomization until death (up to approximately 47 months)
Percentage of Participants Who Received Breast-Conserving Surgery (BCS)	BCS rate was defined as the percentage of participants who achieve BCS out of the ITT population of participants without inflammatory breast cancer.	Surgery performed after completion of neoadjuvant therapy (approximately 6 months after neoadjuvant period)
Event-Free Survival	Event-free survival (EFS) is defined as the time from randomization to disease progression or disease recurrence (local, regional, distant, or contralateral, invasive or non-invasive), or death from any cause. 3 years EFS rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment.	From randomization up to disease progression or recurrence or death (up to approximately 47 months)
Invasive Disease-free Survival (IDFS)	IDFS is defined only for participants who undergo surgery. IDFS is defined as the time from surgery to the first documented occurrence of an IDFS event, defined as: Ipsilateral invasive breast tumor recurrence; Ipsilateral local-regional invasive breast cancer recurrence; Distant recurrence; Contralateral invasive breast cancer; and death from any cause. 3 years of IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment.	From surgery to the first documented occurrence of IDFC event (up to approximately 47 months)
Percentage of Participants by Response for Neuropathy Single Item	Participants answered the question "Did you have tingling hands/feet?", from the Modified Quality of Life Questionnaire Breast Cancer 23 (mQLQ-BR23), on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported.	Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months)
Percentage of Participants by Response for Skin Problem Single Items	Participants answered the Question 1 "Did itching skin bother you?" and Question 2 "Have you had skin problems?", from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported.	Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months)
Percentage of Participants With a Clinically Meaningful Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Score	Participants rated their quality of life (global health status) on European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ- C30), with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Clinically meaningful deterioration in GHS/QoL was defined as a decrease in score of 10 points in GHS/QoL.	From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
Time to Clinically Meaningful Deterioration in GHS/QoL Score	Participants rated their quality of life (global health status) on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by GHS/QoL. All valid GHS/QoL questionnaires of the neoadjuvant phase including surgery were used. Participants without deterioration were censored at the time of completing the last GHS/QoL plus 1 day. Median time to deterioration was estimated with Kaplan-Meier method. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley.	From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
Time to Clinically Meaningful Deterioration in Function Subscale	Participants rated their function on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by physical function; to first 14-point (or greater) decrease as measured by role function, to first 7-point (or greater) decrease as measured by cognitive function. Median time to deterioration was estimated with Kaplan-Meier method. The 95% CI for the median was computed using the method of Brookmeyer and Crowley.	From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
Maximum Observed Serum Concentration (Cmax) of Trastuzumab	Only participants who received trastuzumab were to be analyzed for this outcome.	15-30 minutes (min) post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period
Cmax of Trastuzumab Emtansine and Total Trastuzumab	Only participants who received trastuzumab emtansine were to be analyzed for this outcome.	15-30 min post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period.
Minimum Observed Serum Concentration (Cmin) of Trastuzumab	Only participants who received trastuzumab were to be analyzed for this outcome.	Pre-study treatment infusion (0 hours [hr]) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period
Cmin of Trastuzumab Emtansine and Total Trastuzumab	Only participants who received trastuzumab emtansine were to be analyzed for this outcome.	Pre-study treatment infusion (0 hr) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period
Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations	DM1 is the metabolite of trastuzumab emtansine. Only participants who received trastuzumab emtansine were to be analyzed for this outcome.	15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1)		15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period
Percentage of Participants With ATA to Trastuzumab		Baseline (Pre-trastuzumab [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (Pre-trastuzumab infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period
Percentage of Participants by Response for Hair Loss Single Item	Participants answered the Question "Have you lost any hair?", from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported.	Baseline,Cycle(C) 3, C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4(approx 47 months)
Percentage of Participants With Selected Adverse Events (AEs)	Selected AEs included hepatotoxicity, pulmonary toxicity, cardiac dysfunction, neutropenia, thrombocytopenia, peripheral neuropathy, hemorrhage, infusion related reaction (IRR)/hypersensitivity, IRR/Hypersensitivity symptoms, rash, diarrhea and mucositis. An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.	Baseline to end of study (approximately 47 months)
Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales	Participants rated their function on EORTC QLQ C-30, with total score and single-item (physical, cognitive and role functioning) scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Clinically meaningful deterioration was defined as a decrease in score of 10 points in physical function; decrease of 7 points in cognitive function and decrease of 14 points in role function.	From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1	Participants were considered post-baseline ATA positive if they had ATAs post-baseline that were either treatment-induced or treatment-enhanced. Participants had treatment-induced ATAs if they had a negative or missing ATA result at baseline, and at least one positive ATA result post-baseline. Participants had treatment-enhanced ATAs if they had a positive ATA result at baseline, and at least one positive ATA result post-baseline that was greater than or equal to (>/=) 0.60 titer units higher than the result at baseline.	Baseline (b) (Pre-TDM1 [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (pb) (Pre-TDM1 infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales	Participants rated their symptoms on EORTC QLQ C-30 and mQLQ-BR23, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates greater degree of symptoms. Clinically meaningful increase in symptoms was defined as an increase in score (deterioration) of 11 points in nausea and vomiting, pain, dyspnea; increase of 9 points in insomnia; increase of 14 points in appetite loss; increase of 15 points in diarrhea, constipation; increase of 10 points in fatigue, systemic therapy side effects, hair loss.	From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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, Symmans WF, Thompson AM, Slamon D. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol. 2019 Sep 1;37(25):2206-2216. doi: 10.1200/JCO.19.00882. Epub 2019 Jun 3.
• Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Beckmann MW, Afenjar K, Fresco R, Helms HJ, Xu J, Lin YG, Sparano J, Slamon D. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):115-126. doi: 10.1016/S1470-2045(17)30716-7. Epub 2017 Nov 23.

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2014
• Primary Completion (Actual): December 31, 2015
• Study Completion (Actual): May 29, 2018

Study Registration Dates

• First Submitted: May 2, 2014
• First Submitted That Met QC Criteria: May 2, 2014
• First Posted (Estimate): May 6, 2014

Study Record Updates

• Last Update Posted (Actual): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 25, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Docetaxel; Carboplatin; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine; Pertuzumab
• Other Study ID Numbers: BO28408; TRIO021 (Other Identifier: Roche); 2012-004879-38 (EudraCT Number)