Add Taxane to Adjuvant Chemo for Early, Node-Negative Breast Cancer

[Hopeful]

Elsevier Global Medical News. 2010 Dec 1, MA Moon

Adding a taxane to anthracycline-based adjuvant chemotherapy improves disease-free survival in women with high-risk but node-negative, early-stage breast cancer, according to a Dec. 2 report in the New England Journal of Medicine.

Such a regimen reduced the risk of recurrence by 32% during a median follow-up of 77 months in the Spanish Breast Cancer Research Group (GEICAM 9805) phase III clinical trial, compared with a regimen that did not contain a taxane, said Dr. Miguel MartÃ*n of Gregorio Marañon University General Hospital, Madrid, and his associates.

The findings indicate that adjuvant taxane therapy may be as beneficial at an early stage of disease as it is known to be at later stages of disease. Moreover, the disease-free survival benefit was consistent across many subgroups of patients, regardless of the tumor's hormone-receptor status, the woman's menopausal status, or the number of high-risk factors, they noted.

A longer follow-up period will be needed to determine whether this benefit translates into improved overall survival, because the number of deaths to date has been too small to make that calculation.

Dr. MartÃ*n and his colleagues undertook this study because until now, the role of taxane therapy in node-negative, early breast cancer has been "undefined." Taxanes are effective against node-positive disease, but there has been "little guidance about taxane use" in this patient group, even though the majority of patients with operable disease at diagnosis have node-negative, early-stage disease.

They performed the open-label study, which was sponsored by Sanofi-Aventis, in 1,060 patients who were treated at 55 medical centers in Spain, Germany, and Poland in 1999-2003. All study subjects had undergone primary surgery for unilateral operable breast carcinoma of stage T1, T2, or T3, and all had negative axillary lymph nodes. All the women had at least one high-risk factor, such as tumor size greater than 2 cm, negative estrogen-receptor or progesterone-receptor status, tumor histologic grade of 2 or 3, or patient age of 35 years or older.

The patients were randomly assigned to receive six 21-day cycles of adjuvant therapy with either a taxane-plus-anthracycline regimen (docetaxel, doxorubicin, and cyclophosphamide) or a nontaxane regimen (fluorouracil, doxorubicin, and cyclophosphamide). There were 539 patients in the taxane (TAC) group and 521 in the fluorouracil (FAC) group. To date, patients have been followed for up to 10 years, with a median follow-up of 6.4 years.

The primary end point (disease-free survival) was achieved by 87.8% of the TAC group, compared with 81.8% of the FAC group. "This corresponds to a 32% reduction in the risk of having an event" such as a relapse, a new primary cancer, or death (hazard ratio, 0.68), the investigators said (N. Engl. J. Med. 2010;363:2200-10).

The estimated 5-year disease-free survival rate was 90.1% with TAC and 85.3% with FAC. The number of patients who would need to be treated with a taxane regimen to prevent one recurrence was 17.

Treatment benefit was seen across all subgroups of patients, regardless of whether or not patients received radiation therapy and regardless of the type of surgery they had.

The rate of grade 3 or 4 adverse events was significantly higher in the taxane group (28.2%) than in the nontaxane group (17%), as was the rate of serious adverse events (22.4% vs 4.2%, respectively). Similarly, the rate of treatment discontinuation was significantly higher in the TAC group (4.7%) than in the FAC group (0.8%).

During the study, the researchers noted that more than 25% of patients taking the taxane regimen were developing neutropenic fever. Primary prophylaxis using granulocyte colony-stimulating factor (G-CSF) was instituted; the TAC group was already receiving prophylactic antibiotic therapy. This strategy of dual prophylaxis ameliorated most TAC-induced toxic effects, Dr. Martin and his associates noted.

This study was funded by GEICAM and Sanofi-Aventis. Data collection, data maintenance, and statistical analyses were performed by Sanofi-Aventis. No other financial conflicts of interest were reported.

Hopeful

PS - I think there is a misprint in the following sentnece: "All the women had at least one high-risk factor, such as tumor size greater than 2 cm, negative estrogen-receptor or progesterone-receptor status, tumor histologic grade of 2 or 3, or patient age of 35 years or older. " I would think the high risk patients would be 35 years or younger.