Phase 3
N=1,486
A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)
Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01772472 ↗Enrolled (actual)
1,486
Serious AEs
10.4%
Results posted
Oct 2019
Primary outcome: Primary: Invasive Disease-free Survival (IDFS) Rate at 3 Years — 77.12; 88.44 percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- trastuzumab (Drug); trastuzumab emtansine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Jul 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Invasive Disease-free Survival (IDFS) Rate at 3 Years |
77.12; 88.44 | <0.0001 sig |
| SECONDARY IDFS Including Second Primary Non-breast Cancer (SPNBC) Rate at 3 Years |
76.98; 87.87 | <.0001 sig |
| SECONDARY IDFS Including SPNBC Rate at 7 Years |
66.19; 79.81 | <0.0001 sig |
| SECONDARY IDFS Including SPNBC Rate at 8 Years |
63.65; 77.76 | <.0001 sig |
| SECONDARY Disease-free Survival (DFS) Rate at 3 Years |
76.98; 87.59 | <0.0001 sig |
| SECONDARY DFS Rate at 7 Years |
66.03; 79.37 | <0.0001 sig |
| SECONDARY DFS Rate at 8 Years |
63.49; 77.14 | <.0001 sig |
| SECONDARY Overall Survival (OS) Rate at 5 Years |
87.71; 91.40 | 0.0082 sig |
| SECONDARY OS Rate at 7 Years |
84.38; 89.07 | 0.0082 sig |
| SECONDARY OS Rate at 8 Years |
81.91; 87.16 | 0.0082 sig |
| SECONDARY Distant Recurrence-free Interval (DRFI) Rate at 3 Years |
83.26; 89.95 | <0.0001 sig |
| SECONDARY DRFI Rate at 7 Years |
76.22; 84.55 | <0.0001 sig |
| SECONDARY DRFI Rate at 8 Years |
74.28; 83.82 | <.0001 sig |
| SECONDARY Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
93.3; 98.8; 8.1; 12.7 | — |
| SECONDARY Percentage of Participants With Cardiac Events as Adjudicated by the Cardiac Review Committee |
4.2; 3.1 | — |
| SECONDARY Percentage of Participants With Hepatotoxicity Events as Adjudicated by the Hepatic Review Committee |
0.1; 0.5 | — |
| SECONDARY Number of Participants Who Discontinued Treatment Due to AEs |
15; 134 | — |
| SECONDARY Number of Participants With AEs and SAEs Leading to Death |
0; 1 | — |
| SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) |
7.9; 7.1; 1.0; 6.5; -0.5; 2.9 | — |
| SECONDARY Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) |
69.8; 67.5; 1.5; 4.6; 3.4; 5.7 | — |
| SECONDARY Serum Concentrations of Trastuzumab Emtansine |
NA; 63.0; 67.4; 1.69; 1.73; 68.5 | — |
| SECONDARY Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) |
NA; 4.21; 3.44; 0.372; 4.81; 3.70 | — |
| SECONDARY Serum Concentrations of Trastuzumab |
NA; 208; 64.8; 218; 58.7 | — |
| SECONDARY Serum Concentrations of Total Trastuzumab |
NA; 71.8; 81.4; 7.93; 13.7; 76.9 | — |
| SECONDARY Median Duration of Trastuzumab Emtansine Exposure |
10 | — |
| SECONDARY Number of Participants With Positive Anti-drug Antibodies (ADAs) to Trastuzumab Emtansine |
17; 16 | — |
| SECONDARY Number of Participants With Positive ADAs to Trastuzumab |
11; 15 | — |
Summary
This 2-arm, randomized, open-label study will evaluate the efficacy and safety of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor present in the breast or axillary lymph nodes following preoperative therapy. Eligible patients will be randomized to receive either trastuzumab emtansine 3.6 mg/kg or trastuzumab 6 mg/kg intravenously every 3 weeks for 14 cycles. Radiotherapy and/or hormone therapy will be given in addition if indicated.
Eligibility Criteria
Inclusion Criteria
- Adult patient, >/= 18 years of age
- HER2-positive breast cancer
- Histologically confirmed invasive breast carcinoma
- Clinical stage T1-4/N0-3/M0 at presentation (patients with T1a/bN0 tumors will not be eligible)
- Completion of preoperative systemic chemotherapy and HER2-directed treatment consisting of at least 6 cycles of chemotherapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based therapy
- Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as specified in protocol
- Pathological evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy
- An interval of no more than 12 weeks between the date of surgery and the date of randomization
- Known hormone-receptor status
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate hematologic, renal and liver function
- Screening Left ventricular ejection fraction (LVEF) >/= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >/= 55% after completion of neoadjuvant chemotherapy.
- For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of /= 2 peripheral neuropathy
- History of exposure to the following cumulative doses of anthracyclines: Doxorubicin > 240 mg/m2; Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) > 480 mg/m2; For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m2
- Cardiopulmonary dysfunction as defined by protocol
- Prior treatment with trastuzumab emtansine
- Current severe, uncontrolled systemic disease
- Pregnant or lactating women
- Any known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis
- Concurrent serious uncontrolled infections requiring treatment or known infection with HIV
- History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product
Data sourced from ClinicalTrials.gov (NCT01772472). 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.