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
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.