2018 ASCO: Shortening Adjuvant Trastuzumab to 6 Months in Patients With HER2-Positive Early Breast Cancer Is Effective and Reduces Cardiac Toxicities
Persephone, a large phase III randomized noninferiority study conducted in the United Kingdom comparing 6 months to 12 months of trastuzumab (Herceptin) in patients with HER2-positive early breast cancer has found 6 months of trastuzumab to be noninferior to 12 months of the therapy. In addition, cardiac events were reduced in patients on the 6-month regimen compared to those on 12-month treatment: 4% vs 8%, respectively. The study was presented during a press briefing in advance of the upcoming 2018 ASCO Annual Meeting and will be reported by Earl et al at the meeting (Abstract 506).
Study Methodology
The study researchers randomized 4,088 patients with HER2-positive early breast cancer from 152 sites in the United Kingdom. The patients were stratified based on estrogen-receptor status, chemotherapy type, and chemotherapy and trastuzumab timing. Half of the participants took trastuzumab for 6 months and the other half, for 12 months. The women also received chemotherapy (anthracycline-based, taxane-based, or a combination of both) while enrolled in the trial. The women were followed for a median of more than 5 years.
The primary endpoint was disease-free survival from diagnosis (first relapse or death from any cause). Randomizing the patients (1:1) enabled the researchers to assess the noninferiority of 6 months (5% 1-sided significance, 85% power), defining noninferiority as “no worse than 3% below the 12-month arm’s assumed 80% 4-year disease-free survival.” The preplanned definitive disease-free survival analysis required 500 events.
Study Results
At 4.9 years of median follow-up, there were 319 deaths (8%) and 500 disease-free survival events (12%). With a 4-year disease-free survival rate of 89% (95% confidence interval [CI] = 88%–91%) in both arms, the hazard ratio (HR) noninferiority limit was set at 1.29. The calculated hazard ratio was 1.05 (95% CI = 0.88–1.25; 95th percentile = 1.22), demonstrating noninferiority (HR < 1.29) of 6-month trastuzumab (1-sided P = .01).
Congruent results were found for overall survival and for the preplanned disease-free and overall survival landmark analyses (after 6 months of trastuzumab). Heterogeneity was observed in some stratification variables. Cardiac events were reduced in patients on the 6-month arm (4%, compared with 8% of patients on the 12-month arm stopping treatment due to cardiotoxicity [P < .0001]).
The study results demonstrate that 6 months of trastuzumab is noninferior to 12 months of trastuzumab. “Given cardiac and other toxicities during months 7 through 12 of treatment, our results would support a reduction of standard trastuzumab duration to 6 months,” concluded the study authors, though they noted further analysis is warranted before oncologists change practice, especially to identify women who would benefit more from 12 months of trastuzumab.
Commentary
“This is a very important study for helping our patients live longer and live better,” said ASCO President Bruce E. Johnson, MD, FASCO, during the press briefing. “This was a government-supported study to find out if a shorter duration of therapy can give the same therapeutic result and cause less toxicity. By reducing [trastuzumab] by half [the researchers], were able to cut down on the number of people who had to stop the treatment by half, and we anticipate this will have an effect on cost as well. We think this is an important study for the 12% of women with early-stage HER2-positive breast cancer.”
Funding for this study was provided by the National Institute for Health Research in the United Kingdom. Author conflict of interest disclosures are available at the end of the study abstract.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
