Incorporating docetaxel into anthracycline-based adjuvant chemotherapy for lymph-node-positive breast cancer may improve disease-free survival (DFS), a study has found.
The results of the multicentre phase III study have been published early online in the Journal of the National Cancer Institute.
The Breast International Group (BIG) 02-98 randomised 2,887 women with invasive, operable breast carcinoma to treatment with one of four adjuvant chemotherapy regimens:
- Sequential control arm (four cycles of doxorubicin followed by three of CMF).
- Concurrent control arm (four cycles of doxorubicin plus intravenous cyclophosphamide, followed by three cycles of CMF).
- Sequential docetaxel arm (three cycles of doxorubicin, three of docetaxel, then three of CMF).
- Concurrent docetaxel arm (four cycles of doxorubicin plus intravenous docetaxel, followed by three cycles of CMF).
Randomisation was stratified according to number of positive lymph nodes (1–3 vs =4), and age (<50 years vs =50 years).
After chemotherapy was complete, tamoxifen (20mg daily for five years) was commenced for those with hormone receptor-positive tumours (the trial preceded the use of adjuvant trastuzumab).
The primary endpoint was DFS; secondary endpoints included overall survival (OS) and toxicity.
The primary analysis evaluated the effect of the addition of docetaxel regardless of the schedule of administration – ie, sequential docetaxel plus concurrent docetaxel treatments vs sequential control plus concurrent control treatments.
Due to a lower-than-anticipated relapse rate, the analysis reported here was performed after five years with 732 DFS events (originally planned after 1,215 events).
The median age of participants was 49 years (range 21–70 years) and more than half (55%) had undergone a mastectomy. The median number of positive lymph nodes was three and the breast cancer was hormone receptor–positive in 76% of cases.
The main results (intention-to-treat) were:
- Overall, adding docetaxel resulted in improved DFS of borderline statistical significance (HR of a DFS event = 0.86, 95% CI 0.74–1.00; p = 0.05).
- DFS was better in the sequential docetaxel arm than the sequential control arm (HR 0.79, 95% CI 0.64–0.98; p = 0.035).
- DFS was similar in the concurrent docetaxel and the concurrent control arms (HR 0.93, 95% CI 0.75–1.14; p = NS).
- DFS was better (borderline) in the sequential docetaxel arm than the concurrent docetaxel arm (HR 0.83, 95% CI 0.69–1.00).
No differences in OS were seen between the groups, but the authors say this could not be adequately assessed at this analysis as there were relatively few deaths, and additional follow-up was required.
The authors conclude: “Incorporating docetaxel into anthracycline-based chemotherapy resulted in an improvement of DFS that was of borderline statistical significance.