Trastuzumab Emtansine Associated With 3-Year iDFS in Stage I HER2+ Breast Cancer

Three-year invasive disease-free survival was associated with the use of trastuzumab emtansine in patients with HER2-positive breast cancer.

One year of treatment with trastuzumab emtansine (Kadcyla; T-DM1) was associated with improved 3-year invasive disease-free survival (iDFS) for patients with stage I HER2-positive breast cancer, according to the results of the phase 2 ATEMPT trial (NCT04893190) published in the Journal of Clinical Oncology.

The 3-year iDFS rate for those who were treated with T-DM1 was 97.8% (95% CI, 96.3%-99.3%; P < .0001). The 3-year recurrence-free interval (RFI) rate was 99.2% (95% CI, 98.2%-100%). Although the study was not powered to assess the efficacy of combination paclitaxel plus trastuzumab (Herceptin), investigators identified 8 iDFS events that translated to a 3-year iDFS rate of 93.4% (95% CI, 88.7-98.2) for for T-DM1. Additionally, the RFI for patients enrolled to receive T-DM1 was 94.3% (95% CI, 89.9%-98.8%).

“Trastuzumab-based therapy is well-established for early-stage, HER2-positive breast cancer. Data from retrospective series of untreated patients with stage I HER2-positive breast cancer suggest that these patients are at a sufficiently high risk of recurrence to warrant systemic therapy, although these patients were predominantly excluded from the pivotal adjuvant trials of trastuzumab,” investigators of the study said.

The study enrolled 512 participants from May 17, 2013, to December 13, 2016, 384 of whom were treated with T-DM1 and 128 received paclitaxel plus trastuzumab. In the T-DM1 arm, 1 patient withdrew consent and was not treated, and in the paclitaxel plus trastuzumab arm, 13 withdrew consent and 1 died before treatment was administered.

The median follow-up time was 3.9 years. The adverse effects (AEs) between both groups differed with grade 2 or lower AEs being more common is the paclitaxel plus trastuzumab arm than the T-DM1. This included neuropathy (23% vs 11%), neutropenia (12% vs 3%), and alopecia (41% vs 0%).

However, thrombocytopenia (11% vs 1%) and elevated bilirubin (5% vs 1%) were higher in the T-DM1 cohort than in the paclitaxel plus trastuzumab arm. Among those who took paclitaxel plus trastuzumab, 23% experienced at least 1 grade 3 or higher AEs vs 16% in the T-DM1 arm. Forty-six percent of patients who were treated with T-DM1 experienced clinically relevant toxicities compared with 47% of those who received paclitaxel plus trastuzumab (P = .83).

In total, 19% and 17% of those in the T-DM1 and trastuzumab arms required dose reduction, respectively. Investigators noted that dose reductions could occur anytime during the 1 year of treatment for patients taking T-DM1, but for patients taking paclitaxel plus trastuzumab, it could only happen during the first 12 weeks.

A higher discontinuation rate was noted for patients who received treatment with T-DM1 (17%) than the paclitaxel plus trastuzumab (6%). Among those who received T-DM1, only 8% discontinued due to AEs that were protocol mandated, while the others were based on physician’s decision. Among those who discontinued treatment with T-DM1 61% crossed over to receive trastuzumab for the remaining year of treatment. The most common reasons for discontinuation in this arm included elevated liver enzymes (28%), neuropathy (19%), and thrombocytopenia (19%).

Of those who were treated with T-DM1, 10 had invasive events or died, 2 had distant recurrences, 2 had local or regional recurrences, 3 had no contralateral primary breast cancer, and 3 died non-breast cancer related deaths.

“Our study found that one year of T-DM1 was associated with few events (only two distant recurrences) in the study population, with a 3-year iDFS [rate] of 97.8%. It is important to acknowledge that this study is not designed to compare efficacy between the 2 arms, and although such a design would be optimal, we felt that it would not be feasible given the low event rate seen in this population with therapy,” the investigators concluded.


Tolaney SM, Tayob N, Dang C, et al. Adjuvant trastuzumab emtansine versus paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT): a randomized clinical trial. J Clin Oncol. 2021;39(21):2375-2385. doi:10.1200/JCO.20.03398

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