Longer-term follow-up of US Oncology's ACTC trial showed that TC (docetaxel/cyclophosphamide) achieved increased overall survival compared with an anthracycline-containing regimen of doxorubicin/cyclophosphamide (AC) as adjuvant therapy for early-stage breast cancer; TC increased survival in older women and those with HER-2 positive early-stage breast cancer.
These new findings were reported at an oral session at the San Antonio Breast Cancer Symposium by Stephen E. Jones, MD, Medical Director and Co-chair of the Breast Cancer Research Committee of the US Oncology Network. The study was supported by Sanofi-Aventis.
“TC is a highly effective, modestly toxic, non-anthracycline adjuvant chemotherapy regimen that should now be considered a standard regimen for early breast cancer. TC deserves further study in new clinical trials,” Dr. Jones stated.
Asked for his opinion, William Gradishar, MD, Professor in the Division of Hematology/Oncology at Northwestern School of Medicine, noted that the data have been presented before and continue to hold up with longer follow-up. The study demonstrates that TC is as good as, and probably better than, AC for women with early stage breast cancer, he said.
“The study does not show that this regimen would be as effective as AC for women with larger tumors and more involved nodes,” though, he added, and TC has the advantage of avoiding cardiac problems associated with anthracyclines.
Dr. Gradishar also pointed out that outcomes with TC were “excellent” in subgroups of women with hormone receptor-positive and -negative tumors and with HER2-positive and -negative tumors.
Study results at a median follow-up of 5.5 years reported in 2006 showed that TC improved the disease-free survival rate by an absolute difference of 6% and overall survival by an absolute difference of 3% compared with AC (Jones S et al: JCO 2006;24:5381–5387). At SABCS, Dr. Jones presented seven-year-follow-up data and reported outcomes in older patients—i.e., women age 65 and over.
The study randomized 1,016 women to four cycles of TC or AC (control arm) following surgery. Patients included in the trial had Stage I, II, or III breast cancer (excluding large tumors). Forty-eight percent of patients had node-negative disease, and 16% were age 65 or older. No neoadjuvant therapy was permitted. The median age of the older group was 68; and for the younger patients, 50.
At seven years of follow-up, disease-free survival was 81% for TC vs 75% for AC, representing a 26% risk reduction for TC. HER-2 status was assessed in 170 patients.
Disease-free survival was superior in the TC arm regardless of whether patients were HER-2 positive or HER-2 negative. In fact, all subgroups also favored TC for disease-free survival, including hormone receptor-negative and hormone receptor-positive subgroups, as well as older and younger subgroups.
At seven years, overall survival was also better in the TC arm: 87% vs 82%, representing a 31% risk reduction for the study arm. Both younger and older patients treated with TC had improved overall survival compared with AC. However, many more deaths without recurrence were reported in the older group, as might be expected by virtue of their age: 12% vs 2%.
Hematologic and nonhematologic toxicities were not significantly different between groups. In the TC arm, Grade 3 or 4 neutropenia occurred in 60% of younger patients (younger than 65) and 52% of older patients (65 and older); in the AC arm, Grade 3 or 4 neutropenia was reported in 54% and 59%, respectively.
Grade 3 or 4 febrile neutropenia was reported in 4.4% of younger patients and 7.7% of older patients treated with TC, and in 2.3% and 3.7%, respectively, in the AC arm.
“There was slightly more febrile neutropenia with TC but more anemia with AC in older patients,” Dr. Jones said. “Fewer long-term toxicities, including cardiac and bone marrow toxicities, were seen with TC.”
Question from Session Co-Moderator
Following Dr. Jones' presentation, session Co-Moderator Eric Winer, MD, Director of the Breast Oncology Center at Dana-Farber Cancer Center, asked Dr. Jones if he had an explanation for why the results were so favorable for TC when another study by Dr. Lori Goldstein et al had shown no benefit for AT vs AC.
Dr. Jones said that higher doses of docetaxel were used in the US Oncology Trial and that there may be more synergy between docetaxel and cyclophosphamide. “This study is the test of time. We now have a survival advantage for TC,” he said.
When asked whether results of this trial have filtered down to the community, Dr. Gradishar said that yes, “there is a slow and steady uptake of TC by community oncologists as a non-anthracycline regimen. It is definitely being used more often in clinical practice.”