The relative risk reduction benefit for both disease-free and overall survival was present and of similar magnitude in virtually all subsets of patients analyzed.
—Edward H. Romond, MD
In the final planned joint analysis of overall survival from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 and North Central Cancer Treatment Group (NCCTG) N9831 trials, the addition of trastuzumab (Herceptin) to paclitaxel following doxorubicin/cyclophosphamide (AC) reduced breast cancer deaths by 37%, according to Edward H. Romond, MD, Professor of Medicine at the University of Kentucky, Lexington.
The studies from the National Surgical Adjuvant Breast and Bowel Project and the North Central Cancer Treatment Group evaluated the benefit of trastuzumab when added to adjuvant chemotherapy for women with HER2-positive early breast cancer. The initial results were reported in 2005 and updated in early 2011. At the 2012 San Antonio Breast Cancer Symposium, Dr. Romond presented the final overall survival analysis.1
Benefit across All Subsets
“The relative risk reduction benefit for both disease-free and overall survival was present and of similar magnitude in virtually all subsets of patients analyzed,” Dr. Romond noted.
In the trials, a regimen of doxorubicin/cyclophosphamide followed by paclitaxel was assigned to 2,028 women, while doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab was assigned to 2,018. The majority of the population had one to three positive lymph nodes, and about half the women were hormone receptor–positive.
At a median follow-up of 8.4 years (data lock as of September 15, 2012), the definitive overall survival analysis was performed after 704 events occurred. About 5% of women assigned to receive trastuzumab did not receive the drug because of cardiac symptoms or decrease in left-ventricular ejection fraction during AC, and 20% assigned to the control arm crossed over to receive trastuzumab after positive results from the first interim analysis; both these groups were included in the intent-to-treat analysis.
Robust Disease-free Benefit
Disease-free survival was 73.7% with doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab vs 62.2% with doxorubicin/cyclophosphamide followed by paclitaxel, for an absolute improvement of 11.5% at 10 years and 40% reduction in risk (P < .0001), Dr. Romond reported.
“This was mostly due to a difference in distant recurrences,” he noted, which were seen in 11.2% and 19.4%, respectively.
Among patients who were hormone receptor–positive, the cumulative incidence of distant recurrence as a first event was 12.7% with doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab and 22.3% with doxorubicin/cyclophosphamide followed by paclitaxel. In the hormone receptor–negative subset, the incidence was 11.9% and 21.5%, respectively.
“For patients with hormone receptor–positive disease, the absolute reduction in the rate of distant recurrence as a first event continues to improve over time with the addition of trastuzumab, and reaches 9.6% at 10 years. For patients with hormone receptor–negative disease, the absolute risk of distant recurrence as a first event is reduced by 9.6% at 7 years, after which distant recurrence from breast cancer is unlikely,” Dr. Romond said.
Deaths Reduced by 37%
Similarly, trastuzumab clearly saved lives. At 10 years, overall survival was 84.0% vs 75.2%, an 8.8% absolute improvement that reflects a 37% reduction in risk (P < .0001). Over time, the difference in survival has widened from 2.9% at 4 years to 5.5% at 6 years and to 7.6% at 8 years. Deaths due to breast cancer were observed in 10.3% of women who received trastuzumab vs 16.8% of those who did not. The risk reduction was of similar magnitude whether patients’ tumors were estrogen and/or progesterone receptor–postive or –negative.
All subgroups benefited from trastuzumab. The absolute differences in overall survival differences were particularly striking for women ≥ 60 years old (13.7%), those with ≥ 10 positive nodes (15.6%), and those with tumors ≥ 5.0 cm (11.8%). ■
Disclosure: Dr. Romond reported no potential conflicts of interest.
1. Romond EH, Suman VJ, Jeong J-H, et al: Trastuzumab plus adjuvant chemotherapy for HER2-positive breast cancer: Final planned joint analysis of overall survival (OS) from NSABP B-31 and NCCTG N9831. 2012 San Antonio Breast Cancer Symposium. Abstract S5-5. Presented December 7, 2012.