In the phase II ATEMPT trial reported in the Journal of Clinical Oncology, Sara M. Tolaney, MD, MPH, and colleagues found that adjuvant trastuzumab emtansine (T-DM1) resulted in “excellent” invasive disease–free survival but did not reduce clinically relevant toxicity compared with paclitaxel/trastuzumab in patients with stage I HER2-positive breast cancer.

Sara M. Tolaney, MD, MPH

Study Details

In the U.S. multicenter trial, 497 evaluable patients enrolled between May 2013 and December 2016 were randomly assigned 3:1 to receive T-DMI at 3.6 mg/kg every 3 weeks for 17 cycles (n = 383) or paclitaxel/trastuzumab (n = 114) consisting of paclitaxel at 80 mg/m² with trastuzumab once every week (4 mg/kg loading dose followed by 2 mg/kg) for 12 weeks followed by trastuzumab for 39 weeks at 6 mg/kg once every 3 weeks. The co-primary objectives were to compare the incidence of clinically relevant toxicities in patients in the T-DM1 vs paclitaxel/trastuzumab groups, and to assess invasive disease–free survival in the T-DM1 group.

Clinically relevant toxicities were defined as grade ≥ 3 nonhematologic toxicity, grade ≥ 2 neurotoxicity, grade ≥ 4 hematologic toxicity, febrile neutropenia, any serious adverse event, and any toxicity that required dose delay or discontinuation of treatment. In assessment of invasive disease–free survival, a 3-year rate of ≤ 95% was considered unsuccessful.

Clinically Relevant Toxicity

Median follow-up was 3.9 years. Clinically relevant toxicities occurred in 46% of patients in the T-DM1 group vs 47% in the paclitaxel/trastuzumab group (P = .83). Among the components of the clinically relevant toxicity endpoint, grade ≥ 3 nonhematologic toxicity occurred in 9% vs 11%, grade ≥ 2 neurotoxicity in 11% vs 23%, grade ≥ 4 hematologic toxicity in 1% vs 0%, febrile neutropenia in 0% vs 2%, toxicity requiring dose delay in 28% vs 26%, treatment discontinuation in 17% vs 6%, and serious adverse events in 3% vs 5%. Overall, grade ≥ 3 adverse events occurred in 16% vs 23% of patients. Symptomatic congestive heart failure occurred in 0.8% vs 1.8% and asymptomatic declines in left ventricular ejection fraction occurred in 0.5% vs 3.5%.

Overall toxicity profiles differed between the two groups. The paclitaxel/trastuzumab group had higher rates of grade ≥ 2 neuropathy (23% vs 11%, P = .003), neutropenia (12% vs 3%, P = .0003), alopecia (41% vs 0%, P < .0001), diarrhea (9% vs 4%, P = .04), gastroesophageal reflux disease (9% vs 4%, P = .04), decreased white blood cell count (6% vs 2%, P = .02), and infusion-related reactions (11% vs 5%, P = .04). The T-DM1 group had higher rates of grade ≥ 2 thrombocytopenia (11% vs 1%, P = .0001) and elevated bilirubin (5% vs 1%, P = .04).

Invasive Disease–Free Survival

Invasive disease–free survival at 3 years in the T-DM1 group was 97.8% (95% confidence interval [CI] = 96.3%–99.3%), rejecting the null hypothesis (P < .0001). The 3-year rate of freedom from invasive local or regional recurrence, distant recurrence, and death from breast cancer was 99.2% (95% CI = 98.2%–100%).

The study was not powered for comparison of invasive disease-free survival in the T-DM1 vs paclitaxel/trastuzumab groups. In the paclitaxel/trastuzumab group, 3-year invasive disease­free survival was 93.4% (95% CI = 88.7%­–98.2%), and the 3-year rate of freedom from invasive local or regional recurrence, distant recurrence, and death from breast cancer was 94.3% (95% CI = 89.9%–98.8%).

The investigators concluded, “Among patients with stage I HER2-positive breast cancer, 1 year of adjuvant T-DM1 was associated with excellent 3-year invasive disease–free survival but was not associated with fewer clinically relevant toxicities compared with paclitaxel/trastuzumab.”

Dr. Tolaney, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.  

Disclosure: The study was supported by the Gloria Spivak Faculty Advancement Fund and by Genentech. For full disclosures of the study authors, visit ascopubs.org.