San Antonio Breast Cancer Symposia Authors: Dr. Sunil Verma Date posted: January 6 th, 2008

Extended follow-up and analysis by age of the US Oncology Adjuvant trial 9735: docetaxel/cyclophosphamide is associated with an overall survival benefit compared to doxorubicin/cyclophosphamide and is well tolerated in women 65 or older Jones S, Holmes F et. al

Background The US Oncology Adjuvant trial 9735 is a randomized trial. Anthracyclines have been a mainstay in the adjuvant therapy of breast cancer over the last decade.There is increasing concern of long-term toxicity associated with anthracyclines especially the risk of cardiac toxicity in the elderly population The previous 5 year follow up results of this trial showed that TC chemotherapy was associated with an improved DFS when compared to AC chemotherapy. The OS benefit was not statistically significant at that time. 7 year follow up results are presented here

R Treatment A: Adriamycin and Cyclophosphamide x 4 cycles Treatment B: Docetaxel and Cyclophosphamide x 4 cycles n=1016 Stage I-III breast ca

Patient Characteristics The average age of patients was around 51 years. About 51% of patients enrolled had node +ve disease with about 11% of them having more than 4 lymph nodes involved.

RESULTS 7 – year results ACTCp-value DFS (%)7581 P=0.03 OS (%)8287 P=0.032

STUDY COMMENTARY At the time of study design, AC was considered a standard regimen for node positive women There is now an overall survival benefit for TC chemotherapy as compared to AC chemotherapy. There was a benefit with TC chemotherapy regardless of age, hormone receptor status and Her-2 receptor status Both regimens were well tolerated in patients regardless of age There were three long term AC treatment related deaths – one case of CHF, myelofibrosis and MDS each.

BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS This is an important study as it provides us with an an effective non- anthracycline alternative for adjuvant therapy in breast cancer About 50% of patients in this trial had node positive disease. Since the inception of this trial we now have more effective chemotherapy regimens compared with AC including dose dense AC followed by Paclitaxel, FEC100, FEC100 followed by docetaxel and so on. We dont have any data as to how TC compares this these third generation regimens. TC may be considered for patients with node negative breast cancer. We may want to consider this as an option for node positive patients where there is a safety concern with anthracyclines. There is now an ongoing clinical trial of TC x 6 cycles vs. TAC for 6 cycles to help confirm these trial results against a third generation chemotherapy regimen.