San Antonio, Texas—Monotherapy with adjuvant trastuzumab emtansine (T-DM1) led to significantly fewer clinically relevant toxicities (CRTs) than paclitaxel plus trastuzumab, but did not meet the preplanned 40% relative reduction in toxicity, according to study findings presented at the 2019 San Antonio Breast Cancer Symposium.

Citing previous study data demonstrating the relationship between adjuvant paclitaxel plus trastuzumab and favorable outcomes in patients with small, HER2-positive breast cancer, Sara M. Tolaney, MD, MPH, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues, conducted the ATEMPT trial to determine whether adjuvant T-DM1 is tied to less toxicity than the combination regimen in this patient population.

They also sought to find out whether use of adjuvant trastuzumab emtansine is associated with a clinically acceptable disease-free-survival (DFS).

The multi-center, phase 2 ATEMPT trial included 512 patients with stage I HER2-positive breast cancer randomized in a 3:1 ratio to receive T-DM1 3.6 mg/kg every 3 weeks for 17 cycles or paclitaxel 80 mg/m² plus trastuzumab once weekly for 12 weeks followed by trastuzumab 6 mg/kg for 39 weeks.

The primary end points of the study were the frequency of CRTs in both treatment arms and DFS in patients receiving T-DM1. CRTs were defined as grade ≥3 nonhematologic toxicity, grade ≥2 neurotoxicity, grade ≥4 hematologic toxicity, febrile neutropenia, and any toxicity that led to a dose delay or therapy discontinuation.

Ultimately, 497 patients initiated the protocol therapy, including 383 given T-DM1 and 114 given paclitaxel plus trastuzumab. Approximately 70%, 10%, 30%, and 60% of patients had tumors that were hormone receptor–positive, T1a, T1b, or T1c, respectively.

There were CRTs reported by 25% of patients receiving T-DM1 and 36% receiving paclitaxel plus trastuzumab—a difference deemed statistically significant by the investigators (P = .03) although the relative rate of reduction was <40% (P = .95). Grade 3/4 neurotoxicity was reported in 9 (2%) patients in the T-DM1 arm versus 8 (7%) patients in the paclitaxel plus trastuzumab arm. Of note, adverse events led to early discontinuation of T-DM1 in 17% of patients.

Across a median follow-up of 3 years, there were 11 DFS events documented in the T-DM1 arm, including 1 case of distant recurrence, 3 local recurrences, 3 contralateral breast cancers, 1 death due to recurrent disease, and 3 deaths from other causes. There were 6 DFS events documented in the paclitaxel plus trastuzumab arm, including 2 cases of distant recurrence, 3 local recurrences, and 1 contralateral breast cancer.

Findings demonstrated a 3-year DFS of 97.5% (95% CI, 95.9%-99.3%) for recipients of T-DM1 versus 93.2% (95% CI, 88.1%-98.7%) for recipients of paclitaxel plus trastuzumab.

“This represents the first report of patients receiving T-DM1 monotherapy as adjuvant treatment for stage I HER2-positive breast cancer. The regimen was associated with very few recurrences in the study population,” Dr Tolaney and colleagues concluded.

“T-DM1 was associated with significantly fewer CRT than paclitaxel plus trastuzumab, but did not meet the preplanned 40% relative reduction in toxicity,” they added.—Hina Porcelli

Tolaney SM, Trippa L, Barry W, et al. TBREAST CANCERRC 033: A randomized phase II study of adjuvant trastuzumab emtansine (T-DM1) vs paclitaxel (T) in combination with trastuzumab (H) for stage I HER2-positive breast cancer (BC) (ATEMPT). Presented at: the 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS1-05.