TBCRC 033: A Randomized Phase 2 Study of Adjuvant Trastuzumab Emtansine versus Paclitaxel in Combination with Trastuzumab for Stage I HER2+ Breast Cancer (ATEMPT)

The APT trial previously demonstrated that adjuvant paclitaxel plus trastuzumab (TH) is associated with favorable outcomes in patients with small HER2+, node-negative breast cancer.¹ The ATEMPT trial sought to determine if adjuvant trastuzumab emtansine (T-DM1) is associated with less toxicity than TH, and if it is associated with a clinically acceptable disease-free survival (DFS) in patients with stage I HER2+ breast cancer.

ATEMPT is an investigator-initiated, randomized, multicenter phase 2 adjuvant study of T-DM1 versus TH in patients with stage I centrally confirmed, HER2+ breast cancer (immunohistochemistry ≥3 and/or fluorescence in situ hybridization ≥2.0).² Patients were randomized 3:1 to T-DM1 or TH. The coprimary end points were the incidence of clinically relevant toxicities (CRTs) with T-DM1 versus TH and to evaluate DFS in those receiving T-DM1. CRT included grade ≥3 nonhematologic toxicity, grade ≥2 neurotoxicity, grade ≥4 hematologic toxicity, febrile neutropenia, and any toxicity requiring dose delay or discontinuation of protocol therapy. A total of 512 patients with HER2+ breast cancer (and 73% with hormone-receptor positive tumors) were enrolled and 497 patients began protocol therapy (383 T-DM1, 114 TH).

CRTs were experienced by 25% of patients receiving T-DM1 and 36% of patients receiving TH; the difference was statistically significant (P = .03) but the relative reduction was <40% (P = .95). Two percent (9/383) of patients receiving T-DM1 experienced grade 3/4 neurotoxicity compared with 7% (8/114) of patients receiving TH; 17% of patients discontinued T-DM1 early due to adverse events. With 1562 patient-year follow-up and a median follow-up of 3.0 years, a total of 11 DFS events in the T-DM1 arm and 6 events in the TH arm have occurred. The 3-year DFS for patients receiving T-DM1 was 97.5%; it was was 93.2% for patients receiving TH.

Stating that this was the first report of patients receiving T-DM1 monotherapy as adjuvant treatment for stage I HER2+ breast cancer, the authors reported that the regimen was associated with very few recurrences in the study population. T-DM1 was associated with significantly fewer CRTs than TH but did not meet the preplanned 40% relative reduction in toxicity.

References

1. Tolaney SM, et al. ASCO 2017. Abstract 511.
2. Tolaney SM, et al. SABCS 2019. Abstract GS1-05.