Updated 30 April 2009
Adjuvant therapy of high risk HER2 overexpressing breast cancer
Treatment Options:
1. For newly diagnosed early breast cancer – AC x 4 followed by paclitaxel/trastuzumab (Herceptin®) concurrently for 4 cycles followed by trastuzumab continued for a total of one year of trastuzumab therapy. (BRAJACTT , BRJACTTG)
2. For newly diagnosed locally advanced breast cancer – AC x 4 followed by concurrent docetaxel/trastuzumab followed by trastuzumab continued for total of one year of trastuzumab therapy. (BRLAACDT)
For those who completed chemotherapy after July 1, 2004 (BRAJTR)
Eligibility:
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High risk early and locally advanced breast cancer with the invasive cancer showing overexpression of HER2
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HER-2 positive is defined as either IHC 3+ or FISH ratio of > 2 done in a central laboratory
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High risk is defined as either node positive or node negative with tumours > T1c with other features to qualify for chemotherapy with either AC-paclitaxel, AC-docetaxel, or at least four cycles of anthracycline based chemotherapy
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ECOG 0-2
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No clinically significant cardiac disease
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LVEF of > 55% after the AC portion of the chemotherapy or if being given sequentially after the completion of chemotherapy
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Adequate marrow, renal and hepatic function
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Anticipated survival of at least 5 years
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Being treated or treated within last three months for cure with adjuvant chemotherapy
Not Eligible:
Patients who are not candidates for chemotherapy and are being treated with hormonal therapy only are not candidates for trastuzumab as there is no evidence at this time for the addition of trastuzumab to hormonal treatment in low risk disease.
Letter to the patient
Laboratory
As per the protocols, CBC, diff and platelets should be done 3 weekly. Chemistry should be done if clinically indicated.
Cardiac Monitoring
MUGA scans or Echo cardiograms should be done prior to trastuzumab and at 3 monthly intervals during therapy and at completion of therapy. The following schema should be followed.
Asymptomatic Patients
Rules for Trastuzumab Continuation Based on Serial LVEFs
|
Relationship of
LVEF to LLN |
Absolute
Decrease
Of < 10% |
Absolute
Decrease
Of 10 -15% |
Absolute
Decrease
Of > 16% |
|
Within Normal Limits |
Continue |
Continue |
Hold * |
|
1-5% below LLN |
Continue |
Hold * |
Hold * |
|
> 6 % below LLN |
Continue * |
Hold * |
Hold * |
-
Repeat LVEF assessment after 4 weeks
-
If criteria for continuation are met – resume trastuzumab
-
If 2 consecutive holds or a total of 3 holds occur, discontinue trastuzumab
Symptomatic Patients
Schedule:
AC can be given either every two weeks or every three weeks. Paclitaxel and Docetaxel should be given three weekly. For patients on three weekly protocols and after chemotherapy trastuzumab should be given three weekly.
Radiation:
For patients with indications for radiation, it should be given at the usual time after the completion of the chemotherapy. The trastuzumab should be continued during the radiation therapy. There has been no increased toxicity reported in the clinical trials at this time, but the patients should be monitored as there is not long term data yet. Internal mammary irradiation should be used with caution, when combined with herceptin.
Hormonal therapy:
Hormone therapy should be started in women with hormone sensitive disease after the completion of the chemotherapy and/or radiation. The choice of endocrine therapy should be based on the woman's menstrual status and risk factors. The majority of the patients in the trials received tamoxifen and there is no data that it is not effective in this setting with concurrent trastuzumab.
Pregnancy and Lactation:
The safety of Herceptin in pregnancy is not fully established. As it is a large antibody it does not likely cross the placenta and has been given in pregnancy in critical situations. As per other recommendations during pregnancy, if necessary it can be given but its safety is less well studied than in non-pregnant women and if possible delivery of the baby is optimal before treatment.
Key evidence:
1. Joint Analysis of Intergroup 9831 and NSABP B31.
2. HERA first interim analysis.
Advantages to new treatment:
1. Joint Analysis showed improved OS, DFS.
2. HERA Analysis showed improved DFS, DDFS, Survival Data pending.
Patients with her2/neu overexpression have been observed to have a higher than usual risk of developing CNS metastases. The CNS is a sanctuary site, unreached by most adjuvant systemic agents. There is little or no data to guide physicians in the circumstance of a patient developing isolated CNS metastasis while on adjuvant therapy with a trastuzumab-containing regimen. In various cancer settings, some individuals who develop isolated metastases, who are managed with aggressive local therapy and systemic treatment as appropriate, may yet obtain durable remissions. In view of this, BTG members would propose that, if a patient develops limited and isolated CNS metastases while on an adjuvant trastuzumab regimen, resection of metastases and CNS radiation should proceed if feasible. If all visible disease has been resected, providing a chance of long-term remission, then it would be up to the discretion of the treating oncologist whether to continue to complete the intended year of adjuvant trastuzumab. Alternately, patients could suspend therapy with trastuzumab at that time, and resume it at the time that non-CNS metastases were detected. If, at the time of presentation with CNS metastases on therapy, there were metastases also found outside the CNS, trastuzumab therapy should be discontinued and not restarted.