Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31

Abstract

Purpose: Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). The clinical benefits of adjuvant trastuzumab have been demonstrated in interim analyses of four large trials. Initial data of the combined analysis of the North Central Cancer Treatment Group (NCCTG) N9831 Intergroup trial and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial were reported in 2005. Long-term follow-up results on disease-free survival (DFS) and overall survival (OS) have been awaited.

Patients and methods: Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab in the NCCTG N9831 and NSABP B-31 trials. The similar design of both trials allowed data from the control and trastuzumab-containing arms to be combined in a joint analysis.

Results: At 3.9 years of median follow-up, there continues to be a highly statistically significant reduction in DFS event rate in favor of the trastuzumab-containing arm (P < .001). Similarly, there continues to be a statistically significant 39% reduction in death rate in favor of the trastuzumab-containing arm (P < .001).

Conclusion: These data demonstrate consistent DFS and OS advantages of adjuvant trastuzumab over time, with the longest follow-up reported to date. The clinical benefits continue to outweigh the risks of adverse effects.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

CONSORT diagram. HER2, human epidermal growth factor receptor 2; q3w, every 3 weeks; w, weeks.

Fig 2.

Trial schema of North Central Cancer Treatment Group (NCCTG) N9831 and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31. Timing of chemotherapy, trastuzumab (H), radiation therapy (RT), and hormonal therapy (HT) in B-31 and N9831. AC, doxorubicin and cyclophosphamide; FISH, fluorescent in situ hybridization; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; LVEF, left ventricular ejection fraction; q3w, every 3 weeks; qw, every week; T, paclitaxel.

Fig 3.

Kaplan-Meier estimates of (A) event-free survival and (B) overall survival. Disease events include local, regional, or distant recurrence; contralateral breast cancer; second primary cancers; or death as a result of any cause. Overall survival is measured from the time of study enrollment to last contact or death. AC, doxorubicin and cyclophosphamide; H, trastuzumab; T, paclitaxel.

Fig A1.

Disease event incidence rate. AC, doxorubicin and cyclophosphamide; H, trastuzumab; T, paclitaxel.

Fig A2.

Forest plots. ER, estrogen receptor; PR, progesterone receptor.