Phase 3
Completed N=444
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
Source: ClinicalTrials.gov NCT02131064 ↗Enrolled (actual)
444
Serious AEs
22.6%
Results posted
Jun 2017
Primary outcomePrimary: Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples — 56.1; 44.4 Percentage of Participants — p=0.0126
◆ Published Evidence
Highly cited
526citations · ~66 / year
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.
Summary
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.
Linked Publications (3)
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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.
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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.
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Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples |
56.1; 44.4 | 0.0126 sig |
| SECONDARY Overall Survival |
97.6; 97.0 | 0.7557 |
| SECONDARY Percentage of Participants Who Received Breast-Conserving Surgery (BCS) |
52.6; 41.7 | 0.0228 sig |
| SECONDARY Event-Free Survival |
94.21; 85.28 | 0.0027 sig |
| SECONDARY Invasive Disease-free Survival (IDFS) |
91.99; 93.04 | — |
| SECONDARY Percentage of Participants by Response for Neuropathy Single Item |
78.7; 81.2; 9.5; 9.4; 0; 0 | — |
| SECONDARY Percentage of Participants by Response for Skin Problem Single Items |
71.9; 72.6; 14.9; 16.1; 0; 0 | — |
| SECONDARY Percentage of Participants With a Clinically Meaningful Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Score |
69.9; 45.4 | — |
| SECONDARY Time to Clinically Meaningful Deterioration in GHS/QoL Score |
3.02; 4.63 | 0.0001 sig |
| SECONDARY Time to Clinically Meaningful Deterioration in Function Subscale |
2.79; 4.86; 2.79; 4.44; 3.42; 4.44 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of Trastuzumab |
167; 148; 159; 181 | — |
| SECONDARY Cmax of Trastuzumab Emtansine and Total Trastuzumab |
80.4; 71.7; 79.1; 79.1; 70.4; 73.1 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) of Trastuzumab |
45.8; 21.8 | — |
| SECONDARY Cmin of Trastuzumab Emtansine and Total Trastuzumab |
3.04; 12.3; 4.09; 8.70 | — |
| SECONDARY Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations |
4.64; 4.73; 4.49; 5.15 | — |
| SECONDARY Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) |
8.18; NA; 8.22; NA; 7.98; NA | — |
| SECONDARY Percentage of Participants With ATA to Trastuzumab |
11; 2.6; 5.4; 5.0 | — |
| SECONDARY Percentage of Participants by Response for Hair Loss Single Item |
81.4; 87.4; 7.7; 4.0; 0; 0 | — |
| SECONDARY Percentage of Participants With Selected Adverse Events (AEs) |
14.2; 39.0; 0.9; 4.9; 4.6; 1.3 | — |
| SECONDARY Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales |
59.1; 42.4; 72.5; 40.0; 76.7; 47.8 | — |
| SECONDARY Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1 |
5.5; 7.5; 11.7; 13.1 | — |
| SECONDARY Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales |
61.1; 47.8; 91.2; 40.5; 89.7; 75.1 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02131064) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.