VIENNA – One year of adjuvant trastuzumab after primary therapy for HER2-positive early breast cancer remains the recommended standard of care, according to the first report of a landmark analysis from the HERA trial and findings from the PHARE study.
The latest data to emerge from the HERA (Herceptin Adjuvant) trial show similar disease-free survival and overall survival for 1 and 2 years of adjuvant trastuzumab (Herceptin), with respective hazard ratios (HRs) of 0.99 (95% confidence interval, 0.85-1.14; P =.86) and 1.05 (95% CI, 0.86-1.28; P = .63).
In the PHARE (Protocol of Herceptin Adjuvant With Reduced Exposure) study, which was designed as a noninferiority trial, disease-free survival at 1, 2, 3, and 4 years was not statistically different for those given 6 months versus 1 year of adjuvant trastuzumab. The respective disease-free survivals at 4 years were 84.9% and 87.8%, with an HR of 1.28 (95% CI 1.05-1.56, P = .29).
"In my opinion, 1 year adjuvant trastuzumab is still considered the standard of care," ASCO president Dr. Barbara Swain commented.
Dr. Swain, who is the director of the Washington Cancer Institute, was the invited discussant for the trials after their presentation, Oct. 1, at the European Society for Medical Oncology Congress.
"It’s very important that the presented data be peer reviewed and certainly longer follow-up for PHARE be obtained before final conclusions can be made," she added.
HERA Now at 8-Years’ Follow-up
To date, HERA has been the only trial to look at whether prolonging trastuzumab for more than 1 year may further increase patient survival. The trial findings, which were originally published in 2005 (N. Engl. J. Med. 2005;353:1659-72), showed that 1 year of treatment after adjuvant chemotherapy significantly improved disease-free survival among women with HER2-positive breast cancer.
Now with a median of 8 years of follow-up, the HERA investigators were able to report on the 2-year versus 1-year comparison, using a landmark analysis that considered 3,105 women who had remained disease free for at least 1 year since being randomized to trastuzumab.
Disease-free survivals for 2 years versus 1 year of trastuzumab were comparable, at 89.1% and 86.7%, respectively, at 1 year; 81.6% and 81.0% at 5 years; and 75.8% and 76.0% at 8 years.
Sara Freeman/IMNG Medical Media
Dr. Richard Gelber
Disease-free survivals according to hormone receptor status were also comparable, although an intriguing finding was that there was a slight difference in disease-free survival favoring 2 years of trastuzumab in HR-negative women at about the 3-year mark.
"This raises hypotheses and illustrates the need to evaluate results by receptor status," Richard Gelber, Ph.D., one of the biostatisticians for the HERA trial, commented at a press briefing.
Looking at safety, secondary cardiac end points and other adverse events were increased in the 2-year trastuzumab arm, with 7.2% of patients having a decreased left ventricular ejection fraction versus 4.1% of those treated for 1 year, and 0.9% of those who were in the observation arm.
"Today, I am happy to report that the overall survival advantage for trastuzumab versus observation is sustained, it’s robust, and it’s long term," said Dr. Gelber, of the Dana-Farber Cancer Institute in Boston.