Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer

1. Invasive disease-free survival occurred in 19.7% of the T-DM1 group and 32.2% in the trastuzumab group, with an HR of 0.54 (significant).

2. Investigator-adjudicated trial-related adverse events of any grade occurred in 3.2% of the T-DM1 group and 1.7% in the trastuzumab group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant therapy face a high risk of recurrence and death. Recent trials demonstrated that adjuvant trastuzumab emtansine (T-DM1) had some improved outcomes compared to trastuzumab in early analysis. This study reported an updated final analysis of adjuvant T-DM1 compared to trastuzumab. The primary outcome was invasive disease-free survival (DFS) and secondary endpoints included overall survival (OS) and safety. DFS occurred in 19.7% in the T-DM1 group and 32.2% in the trastuzumab group, with an HR of 0.54 (significant). The estimated 7-year invasive DFS was 80.8% in the T-DM1 group and 67.1% in the trastuzumab group. Subgroup analysis explored HER2 receptor status and found 7-year invasive DFS in the IHC 3+ cohorts was 82.8% with T-DM1 and 66.5% with trastuzumab (HR 0.47, significant) and in the IHC 2+ cohorts was 72.4% and 68.8%, respectively (HR 0.84, non-significant). Another subgroup analysis found patients with residual invasive disease of 1 cm or less and negative axillary nodes had 7-year invasive DFS of 85.7% with T-DM1 and 76.7% with trastuzumab, with HR 0.62 (non-significant). Regarding OS, the estimated 7-year OS was 89.1% in the T-DM1 group and 84.4% in the trastuzumab group, with HR 0.66 (significant). With regards to safety, adverse events of grade 3 or higher were observed in 26.1% of the T-DM1 group and 15.7% in the trastuzumab group, however, investigator-rated trial-related adverse events of any grade occurred in 3.2% in the T-DM1 group and 1.7% in the trastuzumab group. The strengths of this study include its methodology, sample size, and follow-up time, and the limitations include limited data in specific cohorts. Overall, this study found that T-DM1, as compared with trastuzumab, had some improved outcomes after neoadjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease.

Click to read the study in NEJM

Relevant Reading: Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

In-Depth [randomized controlled trial]: This phase 3 trial enrolled patients with HER2-positive early breast cancer who received at least 6 cycles of neoadjuvant chemotherapy with taxanes/trastuzumab who had residual disease at surgery and then randomized them (1:1) to either T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. Radiation and endocrine therapy were administered according to institutional standards and the trial protocol. Median follow-up was 101.4 months (0.1-123.3) in the T-DM1 group and 100.8 months (0.1-122.8) in the trastuzumab group. DFS occurred in 19.7% of the T-DM1 group and 32.2% in the trastuzumab group, with an HR of 0.54 (95%CI, 0.44-0.66). The estimated 7-year invasive DFS was 80.8% in the T-DM1 group and 67.1% in the trastuzumab group. Subgroup analysis explored HER2 receptor status and found 7-year invasive DFS in the IHC 3+ cohorts was 82.8% with T-DM1 and 66.5% with trastuzumab (HR 0.47 [95%CI, 0.37-0.60]) and in the IHC 2+ cohorts was 72.4% and 68.8%, respectively (HR 0.84 [95%CI, 0.56-1.25]). Another subgroup analysis found patients with residual invasive disease of 1 cm or less and negative axillary nodes had 7-year invasive DFS of 85.7% with T-DM1 and 76.7% with trastuzumab, with HR 0.62 (95%CI, 0.37-1.03). With regards to OS, the estimated 7-year OS was 89.1% in the T-DM1 group and 84.4% in the trastuzumab group, with HR 0.66 (95%CI, 0.51-0.87, p=0.003). With regards to safety, adverse events of grade 3 or higher were observed in 26.1% of the T-DM1 group and 15.7% in the trastuzumab group, however, investigator-rated trial-related adverse events of any grade occurred in 3.2% in the T-DM1 group and 1.7% in the trastuzumab group. Overall, this study found that T-DM1, as compared with trastuzumab, had some improved outcomes after neoadjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease.

Image: PD

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