LONDON -- For early-stage breast cancer that is HER2-positive, a year of adjuvant Herceptin (trastuzumab) significantly improves overall survival two years later without undue cardiotoxicity, researchers here said.
LONDON, Jan. 5 -- For early-stage breast cancer that is HER2-positive, a year of adjuvant Herceptin (trastuzumab) significantly improves overall survival two years later without undue cardiotoxicity, researchers here said.
A year of Herceptin after anthracycline-containing chemotherapy improved overall survival by 2.7% among women in the HERA study, reported Ian Smith, M.D., of the Royal Marsden Hospital, and colleagues, in the Jan. 6 issue of The Lancet.
"The emergence of this benefit after only two years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer," they wrote.
They added, "That the risk of cardiotoxicity remains low is encouraging."
Herceptin, a humanized monoclonal antibody against HER2, has previously been shown in the open-label HERA trial and others to improve disease free survival for women with HER2-positive early breast cancer after standard neoadjuvant or adjuvant chemotherapy.
While widespread adjuvant use ensued, "this use has been criticized by some because the findings arise from interim analyses, follow-up is short, and significant overall survival benefit has not been shown in any stand alone trial," Dr. Smith and coauthors wrote.
To see the effect on the secondary endpoint of overall survival advantage in the HERA trial, the researchers analyzed intent-to-treat data from 1,703 women who received Herceptin for one year and 1,698 in the control group.
All participants had HER2-positive node positive or high-risk node negative breast cancer. Herceptin was given as an 8 mg/kg intravenous loading dose then 6 mg/kg every three weeks.
After a median follow-up of about two years, 59 women in the treatment group and 90 in the placebo group had died (difference 1.8%, 3.5% versus 5.3%). The unadjusted hazard ratio for death in the Herceptin group compared with placebo was 0.66 (95% CI 0.47 to 0.91, P=0.0115). The absolute overall survival benefit was 2.7% (92.4% versus 89.7%) at three years after randomization.
Dr. Smith and colleagues said such survival findings after only two years are unusual among breast cancer treatment trials for any therapy.
"That this survival difference will not be sustained with further follow-up is a possibility," they wrote, though they calculated that the chance of losing significance with longer follow-up was less than 20%.
There were 218 disease-free survival events with Herceptin compared with 321 in the control group. The unadjusted hazard ratio for the risk of an event with Herceptin versus placebo was 0.64 (95% CI 0.54 to 0.76, P
Still, some cardiac problems were seen in the study. The findings were: