Evaluation of Trastuzumab Without Chemotherapy as a Postoperative Adjuvant Therapy in HER2 Positive Elderly Breast Cancer Patients (RESPECT)

• Overall survival [ Time Frame: Patients are followed up for 7 years after initial enrollment (from Oct. 2009 through Oct. 2016). ] [ Designated as safety issue: No ]
  Overall survival is defined as the interval from the date of enrollment to the date of death from any cause.
• Relapse-free survival [ Time Frame: Patients are followed up for 7 years after initial enrollment (from Oct. 2009 through Oct. 2016). ] [ Designated as safety issue: No ]

  Relapse-free survival is defined as the interval from the date of enrollment to the date of any of the following events.

  1. Local recurrence, distant metastasis
  2. Death
• Percentage of participants with adverse events as a measure of safety [ Time Frame: Evaluations are performed at the time of starting the specified treatment and 2, 3, and 6 month, 1 year, 1 year 6 months, 2 years, 2 years 6 months, and 3 years after the start of treatment. Subsequently, evaluations are done at 1-year intervals. ] [ Designated as safety issue: Yes ]
  The following variables are evaluated: left ventricular ejection fraction, white-cell count, neutrophil count, platelet count, bilirubin level, alanine aminotransferase level, aspartate aminotransferase level, alkaline phosphatase level, and creatinine level.
• Health-related QOL (HRQOL) [ Time Frame: Evaluations are performed at the time of starting the specified treatment and 2 months, 1 year, and 3 years after the start of treatment. ] [ Designated as safety issue: No ]
  The following QOL questionnaire forms (in Japanese) are used for evaluations: FACT-G, HADS, EQ-5D, and PNQ.
• Cost effectiveness analysis [ Time Frame: Data on direct medical costs for the 3-year period after the start of the treatment are obtained from CRF. Data on direct nonmedical costs and indirect costs are obtained from questionnaires 2, 12, and 36 months after starting the treatment. ] [ Designated as safety issue: No ]

  Survey items are as follows.

  1. Direct medical costs: medical costs associated with therapy, the management of adverse events, etc.
  2. Direct nonmedical costs: transportation expenses required for medical examinations, costs of health foods, etc.
  3. Indirect costs: work-loss costs associated with treatment that are incurred directly by the patient and by their caregivers

• Overall survival [ Designated as safety issue: No ]
• Relapse-free survival [ Designated as safety issue: No ]
• Percentage of participants with adverse events as a measure of safety [ Designated as safety issue: Yes ]
• Health-related QOL (HRQOL) [ Designated as safety issue: No ]
• Cost effectiveness analysis [ Designated as safety issue: No ]

To investigate clinical positioning between trastuzumab (Herceptin) monotherapy (H group) and combination therapy of trastuzumab and chemotherapy (H+CT group) based on a randomized controlled trial in women over 70 years with human epidermal growth factor receptor type-2 (HER2) positive primary breast cancer.

• Drug: trastuzumab
  • Trastuzumab: 1-year treatment
  • Loading dose, 8 mg/kg; from 2nd dose, 6 mg/kg; iv inj, qw, 18 times "
• Drug: chemotherapy
  • Chemotherapy: 12 to 24 weeks
  • Select chemotherapy from certain regimens (PTX, DTX, TC, AC, EC, FEC and CMF) based on decision of a physician or a patient. Initiate administration of trastuzumab after completion of chemotherapy as a sequential combination. However, concomitant administration is allowed when combining trastuzumab with PTX, DTX and CMF.

• Active Comparator: trastuzumab and chemotherapy
  Interventions:

  • Drug: trastuzumab
  • Drug: chemotherapy
• Experimental: trastuzumab monotherapy
  Intervention: Drug: trastuzumab

Inclusion Criteria:

1. Histologically diagnosed as invasive breast cancer and received curative operation for primary breast cancer.
2. Stage: 1 (tumor size [pT] > 0.5 cm), 2A, 2B or 3A/ M0
3. Female between 69 and 81 years old
4. Primary region is HER 2 positive: either 3+ overexpression by IHC or positive by FISH
5. Baseline left ventricular ejection fraction (LVEF) is ≥55% measured by echocardiography or MUGA scan within 4 weeks before registration.
6. PS: 0-1 (ECOG)

7. Sufficient organ function meeting following criteria within 4 weeks before registration:

   • Leukocyte ≥2500 mm3
   • Neutrophil ≥1500 mm3
   • Platelet ≥100 000 mm3
   • Serum total bilirubin ≤2.0 x upper limit of normal (ULN)
   • ALT (GPT) or AST (GOT) ≤2.5 x ULN
   • Serum creatinine ≤2.0 x ULN
   • ALP ≤2.5 x ULN
8. No previous endocrine therapy or chemotherapy for breast cancer
9. Signed written informed consent (Appendix A)

Exclusion Criteria:

1. Active multiple primary cancer (synchronous multiple primary cancer and invasive cancer of other organs)
2. Postoperative histological axillary lymph node metastasis ≥4
3. Axillary lymph node is not histologically evaluated
4. Histologically confirmed positive margin in breast conservation surgery (evaluation of margin status is based on policy of site)
5. History of drug-related allergy which could hinder planned treatment

6. Any history or complication of following cardiac disorders

   • History of congestive heart failure, cardiac infarction
   • Complication requires treatment such as: ischemic cardiac disorder, arrhythmia, valvular heart disease
7. Poorly controlled hypertension (ex. Systolic arterial pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg)
8. Poorly controlled diabetes
9. Continuous visit to a medial institution is considered difficult due to deterioration of activity of daily living (ADL)
10. Difficult to participate in the trial because of psychiatric disorder or psychiatric symptoms
11. Ineligible to the trial based on decision of an investigator