ASCO Adapts CCO Guideline on Selection of Optimal Adjuvant Therapy for Breast Cancer

By Matthew Stenger
Posted: 4/28/2016 11:29:35 AM
Last Updated: 4/28/2016 11:29:35 AM

ASCO has adapted a Clinical Care Ontario (CCO) clinical practice guideline on the selection of optimal adjuvant chemotherapy for early breast cancer and adjuvant targeted therapy for HER2-positive breast cancer, as reported in the Journal of Clinical Oncology. The adaptation was based on review by an expert ASCO panel co-chaired by Neelima Denduluri, MD, of The US Oncology Network, Virginia Cancer Specialists, Arlington, and Antonio C. Wolff, MD, of The Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.

The adapted ASCO recommendations are reproduced here. Those marked by an asterisk are verbatim from the CCO guideline. Others have been substantively adapted or reworded by the ASCO panel.

Recommendations

• Use of an Anthracycline-Taxane Regimen: In patients who can tolerate it, use of a regimen containing anthracycline/taxane is considered the optimal strategy for adjuvant chemotherapy, particularly for patients deemed to be at high risk.*
• Optimal-Dose Anthracycline Regimen for Patients for Whom a Taxane Is Contraindicated: For patients with high-risk disease who will not receive a taxane, an optimal-dose anthracycline three-drug regimen (cumulative dose of doxorubicin at ≥ 240 mg/m² or epirubicin at ≥ 600 mg/m² but no higher than 720 mg/m²) that contains cyclophosphamide is recommended. The cumulative dose of doxorubicin in two-drug regimens should not exceed 240 mg/m².
• Adding Gemcitabine or Capecitabine to an Anthracycline/Taxane Regimen: The addition of gemcitabine or capecitabine to anthracycline/taxane regimen is not recommended for adjuvant chemotherapy.*
• Capecitabine in Patients Aged ≥ 65 Years: In patients aged 65 years or older, capecitabine is not recommended as an adjuvant chemotherapy option in lieu of standard regimens such as doxorubicin/cyclophosphamide or cyclophosphamide/methotrexate/fluorouracil (with oral cyclophosphamide).
• Cyclophosphamide/Methotrexate/Fluorouracil as an Alternative to Doxorubicin/Cyclophosphamide: For patients in whom anthracycline/taxane is contraindicated, cyclophosphamide/methotrexate/fluorouracil (with oral cyclophosphamide) is an acceptable chemotherapy alternative to doxorubicin/cyclophosphamide. Of note, the ASCO panel recommends classic cyclophosphamide/methotrexate/fluorouracil (oral cyclophosphamide on days 1–14 with IV [intravenous] methotrexate/fluorouracil on days 1 and 8, repeated once every 28 days for six cycles) as the default adjuvant cyclophosphamide/methotrexate/fluorouracil regimen. However, the panel also recognizes that an all-IV cyclophosphamide/methotrexate/fluorouracil regimen once every 21 days is often used in clinical practice and was accepted by some clinical trials (eg, TAILORx) on the basis of convenience and tolerability despite the absence of efficacy data from randomized controlled trials.
• Acceptable Adjuvant Chemotherapy Regimens for Patients With Higher-Risk Early Breast Cancer: These adjuvant chemotherapy regimens can be used for patients with early breast cancer:
• Fluorouracil/epirubicin/cyclophosphamide x 3 → docetaxel x 3 (superior to fluorouracil/epirubicin/cyclophosphamide x 6)
• Doxorubicin/cyclophosphamide x 4 → docetaxel x 4 (superior to doxorubicin/cyclophosphamide x 4)
• Docetaxel/doxorubicin/cyclophosphamide x 6 (superior to fluorouracil/doxorubicin/cyclophosphamide x 6)
• Doxorubicin/cyclophosphamide x 4 → paclitaxel administered once per week
• Dose-dense doxorubicin/cyclophosphamide → paclitaxel administered once every 2 weeks
• Adjuvant Regimen When an Anthracycline Is Not Preferred: Docetaxel/cyclophosphamide x 4 is recommended as an alternative to doxorubicin/cyclophosphamide x 4 and offers improved disease-free and overall survival. Classic cyclophosphamide/methotrexate/fluorouracil with oral cyclophosphamide for six cycles is another option. As mentioned, the ASCO panel recommends classic cyclophosphamide/methotrexate/fluorouracil (oral cyclophosphamide on days 1–14 with IV methotrexate/fluorouracil on days 1 and 8, repeated once every 28 days for six cycles) as the default adjuvant cyclophosphamide/methotrexate/fluorouracil regimen. However, the panel also recognizes that an all-IV cyclophosphamide/methotrexate/fluorouracil regimen once every 21 days is often used in clinical practice and was accepted by some clinical trials (eg, TAILORx) on the basis of its convenience and tolerability despite the absence of efficacy data from randomized controlled trials.
• Patient Selection and Adjuvant Trastuzumab Therapy: Only patients with HER2-positive breast cancer (overexpressed based on immunohistochemistry [3+] or amplified based on in situ hybridization [ratio ≥ 2.0 or average HER2 copy number ≥ 6.0]) should be offered adjuvant trastuzumab.
• Trastuzumab Plus Chemotherapy in Patients With Higher-Risk HER2-Positive Disease: Trastuzumab plus chemotherapy is recommended for all patients with HER2-positive, node-positive breast cancer and for patients with HER2-positive, node-negative breast cancer (> 1 cm).*
• Trastuzumab Plus Chemotherapy in Patients With HER2-Positive T1a-b N0 Disease: Trastuzumab therapy can be considered in small, node-negative tumors (≤ 1 cm).
• Selection of Chemotherapy Regimens in Patients Receiving Trastuzumab: Trastuzumab can be administered with any acceptable adjuvant chemotherapy regimen.*
• Use of Trastuzumab and an Anthracycline-Containing Regimen: The administration of trastuzumab concurrently with the anthracycline component of a chemotherapy regimen is not recommended because of the potential for increased cardiotoxicity.
• Concurrent Administration of Adjuvant Trastuzumab and Nonanthracycline Chemotherapy Regimens: Trastuzumab should be preferentially administered concurrently (not sequentially) with a nonanthracycline chemotherapy regimen.
• Trastuzumab-Based Chemotherapy or Trastuzumab Regimens for Patients at Higher Risk of Cardiotoxicity: Less cardiotoxicity is seen with docetaxel/carboplatin/trastuzumab than with doxorubicin/cyclophosphamide → docetaxel/trastuzumab, and docetaxel/carboplatin/trastuzumab is recommended for patients at higher risk for cardiotoxicity.*
• Addition of Trastuzumab to Chemotherapy Regimens Not Evaluated in a Phase III Trial: No phase III evidence exists for the addition of trastuzumab to some chemotherapy regimens, such as docetaxel/cyclophosphamide. However, those regimens might be in use and are reasonable options, particularly for mitigating cardiotoxicity in certain patients.*
• Duration of Trastuzumab Therapy and Cardiac Function Assessment: Patients should be offered 1 year total of adjuvant trastuzumab, with regular assessments of cardiac function during that period.*

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.