ASCO breast adjuvant guidelines




The latest ASCO guidelines on adjuvant chemotherapy for early breast cancer shows that ICON protocols are in line with international guidelines. ICON’s Dr David Eedes takes us through the important points.

The American Society of Clinical Oncology (ASCO) has issued clinical guidelines on adjuvant chemotherapy for early breast cancer. They also address various important issues regarding targeted adjuvant therapy for HER2-positive breast cancer.

The guidelines are largely adapted from the 2015 Cancer Care Ontario (CCO) clinical practice guidelines, with some additional guidance from ASCO. They were published online on 18 April 2016 in the Journal of Clinical Oncology.

I think the concordance with the ICON Protocols is good and shows that our protocols are in line with international guidelines.

Important Points:

Recommendations taken directly from the CCO guidelines:

-Anthracycline-taxane regimens are the optimal strategy for adjuvant chemotherapy in patients who can tolerate them, especially high-risk patients.

– Adding gemcitabine or capecitabine to an anthracycline-taxane regimen is not recommended.

– Trastuzumab plus chemotherapy is recommended for all patients with HER2-positive node-positive breast cancer and for patients with HER2-positive node-negative breast tumors over 1 cm.

– Trastuzumab can be administered with any acceptable adjuvant chemotherapy regimen.

– Docetaxel-trastuzumab, and docetaxel-carboplatin-trastuzumab are recommended for patients at higher risk for cardiotoxicity; docetaxel-carboplatin-trastuzumab has less cardiotoxicity than doxorubicin-cyclophosphamide.

– No phase three evidence exists for adding trastuzumab to some chemotherapy regimens, like docetaxel-cyclophosphamide. Such regimens might already be in clinical use and represent reasonable options, especially for decreasing cardiotoxicity.

– Patients should be offered one year total of adjuvant trastuzumab; cardiac function should be regularly assessed during that time period.

Recommendations adapted from the CCO guidelines

– In patients with high-risk disease and when a taxane is contraindicated, the optimal dose of an anthracycline three-drug regimen that contains cyclophosphamide is recommended, with a cumulative dose of doxorubicin ≥240 mg/m² or epirubicin ≥600 mg/m², but no higher than 720 mg/m². The cumulative dose of doxorubicin in two-drug regimens should not exceed 240 mg/m².

– Capecitabine is not recommended as adjuvant chemotherapy in patients 65 years and older in lieu of standard regimens, like doxorubicin-cyclophosphamide or oral cyclophosphamide-methotrexate-fluorouracil.

– If anthracycline-taxane is contraindicated, oral cyclophosphamide-methotrexate-fluorouracil is acceptable as an alternative to doxorubicin–cyclophosphamide.

– The default adjuvant cyclophosphamide-methotrexate-fluorouracil regimen should be classic cyclophosphamide-methotrexate-fluorouracil (oral cyclophosphamide on days one to 14 with intravenous [IV] methotrexate–fluorouracil on days one and eight, repeated once every 28 days for six cycles).

– An all-IV cyclophosphamide-methotrexate-fluorouracil regimen once every 21 days is often used in clinical practice and has been accepted by some clinical trials, such as TAILORx (Trial Assigning Individualised Options for Treatment), because of convenience and tolerability, even though efficacy data from randomised controlled trials remain to be seen.

Acceptable adjuvant chemotherapy regimens for patients with higher-risk early breast cancer:

– Fluorouracil-epirubicin-cyclophosphamide × 3 → docetaxel × 3 (superior to fluorouracil-epirubicin-cyclophosphamide × 6).

– Doxorubicin-cyclophosphamide × 4 → docetaxel × 4 (superior to doxorubicin cyclophosphamide × 4).

– Docetaxel-doxorubicin-cyclophosphamide × 6 (superior to fluorouracil–doxorubicin-cyclophosphamide × 6).

– Doxorubicin-cyclophosphamide × 4 → paclitaxel administered once per week.

– Dose-dense doxorubicin-cyclophosphamide → paclitaxel administered once every two weeks.

Adjuvant regimens when an anthracycline is not preferred:

– Docetaxel–cyclophosphamide × 4 is an alternative to doxorubicin–cyclophosphamide × 4 and offers improved disease-free survival and overall survival

– Classic cyclophosphamide–methotrexate–fluorouracil with oral cyclophosphamide for six cycles is another option

– The default adjuvant cyclophosphamide–methotrexate–fluorouracil regimen should be classic cyclophosphamide–methotrexate–fluorouracil (oral cyclophosphamide on days 1 to 14 with IV methotrexate–fluorouracil on days 1 and 8, repeated once every 28 days for six cycles)

– An all-IV cyclophosphamide–methotrexate–fluorouracil regimen once every 21 days is often used in clinical practice and has been accepted by some clinical trials, such as TAILORx, because of convenience and tolerability, even though efficacy data from randomized controlled trials remain to be seen

Notes on targeted adjuvant therapy for HER2-positive breast cancer:

– Adjuvant trastuzumab should be offered only to patients with HER2-positive breast cancer (overexpressed based on immunohistochemistry [3+] or amplified based on in situ hybridisation [ratio ≥2.0 or average HER2 copy number ≥6.0]).

– Trastuzumab plus chemotherapy can be considered in small node-negative HER2-positive tumors ≤1 cm.

– Giving trastuzumab at the same time as the anthracycline component of a chemotherapy regimen is not recommended because of possible increased cardiotoxicity.

– Trastuzumab should be given at the same time as a non-anthracycline chemotherapy regimen, not sequentially.

Reference: Denduluri N, et al. Selection of Optimal Adjuvant Chemotherapy Regimens for Early Breast Cancer and Adjuvant Targeted Therapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers: An American Society of Clinical Oncology Guideline Adaptation of the Cancer Care Ontario Clinical Practice Guideline Published online before print April 18, 2016, doi: 10.1200/JCO.2016.67.0182 JCO April 18, 2016 JCO670182