High-Dose Chemo with Stem Cell Transplant Shows Little to No Survival Benefit in Adjuvant Setting

December 14, 2007

When used as adjuvant therapy for node-positive breast cancer, the combination of high-dose chemotherapy (HDC) and stem cell transplantation modestly improves relapse-free survival relative to standard-dose chemotherapy (SDC). But it offers at best minimal benefit in terms of overall survival, according to a meta-analysis presented at SABCS.

When used as adjuvant therapy for node-positive breast cancer, the combination of high-dose chemotherapy (HDC) and stem cell transplantation modestly improves relapse-free survival relative to standard-dose chemotherapy (SDC). But it offers at best minimal benefit in terms of overall survival, according to a meta-analysis presented at SABCS.

Donald A. Berry, PhD
Photo Courtesy @ SABCS/Todd Buchanan 2007

Donald A. Berry, PhD, and colleagues at the M.D. Anderson Cancer Center and European Group for Blood and Marrow Transplantation analyzed individual patient data from 15 randomized trials among 6210 women with node-positive breast cancer. They were assigned to either HDC with autologous stem cell transplantation or SDC. With a 7-year median follow-up, relapse-free survival was significantly better in the HDC group than in the SDC group in the entire population (hazard ratio, 0.87), but overall survival was not (hazard ratio, 0.94), Dr. Berry said. "Dose intensity varies by trial," he said. "Indeed, some of the trials had higher standard doses than other trials of high dose." In adjusted analyses, a 1-unit increase in average weekly dose intensity conferred a significant but small overall survival benefit (hazard ratio, 0.92). The hazard ratio still overlapped unity for all or nearly all trials, however, when they were plotted by average weekly dose intensity, total dose intensity, and average weekly dose intensity during the high-dose period. "We could not identify subsets of patients that benefit from high-dose therapy," Dr. Berry said. Specifically, HDC had no significant overall survival benefit relative to SDC when women were stratified by age (<50 vs ≥50 years), menopausal status, number of positive nodes (<10 vs ≥10), tumor size (<2 vs ≥2 cm), hormone receptor status (positive vs negative), histology (infiltrating ductal carcinoma vs infiltrating lobular carcinoma), and HER-2/neu status (positive vs negative). Survival after relapse did differ depending on the treatment -- but not in favor of HDC. "If you had standard therapy and relapse, you do better than if you had high-dose therapy," Dr. Berry said. "Maybe the high-dose therapy beats down the visible or surface disease but not the insidious disease any more than does the standard-dose therapy, and when it comes back, it comes back with a vengeance." Another possibility he offered is that HDC is effective in the salvage setting. "There's a modest benefit [of HDC with stem cell transplantation] on relapse-free survival, little or no benefit on overall survival. I think this is the definitive answer," Dr. Berry said. He added that the next step will be to perform similar analyses for trials of this treatment among patients with metastatic breast cancer.

Disclosures:

The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.