Two recent studies in The New England Journal of Medicine (NEJM) focused on the breast cancer drug trastuzumab, a recombinant monoclonal antibody (Herceptin, Genentech/Roche).
Two recent studies in The New England Journal of Medicine(NEJM) focused on the breast cancer drug trastuzumab, a recombinant monoclonal antibody (Herceptin, Genentech/Roche).
Trastuzumab was approved by FDA in 1998 for the treatment of advanced breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2), which is normally involved in the regulation of cell proliferation. To determine the drug's efficacy and safety in the treatment of early-stage breast cancer, 3 groups of researchers studied a total of more than 6,500 women.
In one study, conducted in Belgium, trastuzumab significantly improved disease-free survival among women with HER2-positive breast cancer.
The international, multicenter, randomized Herceptin Adjuvant (HERA) trial consisted of 1,694 women randomly assigned to 2 years of treatment with trastuzumab, 1,694 women assigned to 1 year of the drug, and 1,693 women assigned to observation. The study authors' published report was limited to observing results from patients who received the single year of trastuzumab and the observation group.
At a median follow-up of 1 year, 347 events were observed-127 in the trastuzumab group and 220 in the observation group, with a 0.54 hazard ratio for the former group compared with the latter (95% CI, 0.43–0.67; P<.0001). In terms of disease-free survival at 2 years, this represented an absolute benefit of 8.4 percentage points.
"The results of this trial," the authors stated, "indicate that 1 year of adjuvant trastuzumab should be considered a standard option on completion of locoregional therapy and neoadjuvant or adjuvant chemotherapy for women who fulfill the study eligibility criteria used in the HERA trial."
No significant difference in overall survival was seen in the 2 groups (29 deaths with trastuzumab and 37 with observation). Severe cardiotoxicity developed in 0.5% of the patients treated with trastuzumab.
"We acknowledge that we have only an incomplete picture of the risks associated with trastuzumab," the researchers stated. "The risk of cardiotoxicity is currently low in our trial, but this could change with longer follow-up. Another concern is that longer follow-up may show that trastuzumab is not effective in reducing the incidence of disease recurrence in the central nervous system."
The second study was a combination of 2 trials-the National Surgical Adjuvant Breast and Bowel Project trial B-31 and the North Central Cancer Treatment Group trial N9831-with a joint analysis.
The former group compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks with the same regimen plus 52 weeks of trastuzumab, beginning with the first dose of paclitaxel.
The latter compared 3 regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel, the same regimen followed by 52 weeks of trastuzumab after paclitaxel, and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel. In the combined trials of 3,351 women, 1,672 were in the trastuzumab group, and 1,679 were in the control group.
In total, 394 events were reported: 133 in the trastuzumab group and 261 in the control group (HR=0.48; P<.0001). At 3 years, the absolute difference in disease-free survival between the trastuzumab group and the control group was 12%, and trastuzumab therapy was associated with a 33% reduction in the risk of death (P=.015).
"The addition of trastuzumab to paclitaxel after a regimen of doxorubicin and cyclophosphamide reduced the rates of recurrence by half among women with HER2-positive breast cancer," the authors stated. "The effect of trastuzumab was substantial in both trials, a finding that is noteworthy given differences in the paclitaxel schedule and the timing of hormonal therapy."
An accompanying editorial saw the trials as an important step.
"Clearly, the results reported in this issue of the Journal are not evolutionary but revolutionary," Gabriel N. Hortobagyi, MD, Department of Breast Medical Oncology at the University of Texas M.D. Anderson Cancer Center, Houston, Texas, stated. "The rational development of molecularly targeted therapies points the direction toward continued improvement in breast cancer therapy."
In what Dr Hortobagyi called an "unexpected observation," the 3-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1% in the trial B-31 and 2.9% in trial N9831.
SOURCES Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Eng J Med. 353;16:1659–1672.
Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Eng J Med. 353;16:1673–1684.
Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Eng J Med. 353;16:1734–1736.