‘Outstanding’ Long-Term T-DM1 Data in Early Breast Cancer

TOPLINE:

One year of adjuvant trastuzumab emtansine (T-DM1) leads to an impressive 5-year invasive disease-free survival rate of 97% among women with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer, according to the final analysis of the ATEMPT trial.

METHODOLOGY:

• Long-term outcomes in patients with early HER2-positive breast cancer treated with adjuvant T-DM1 as well as prognostic predictors of recurrence in this population remain unclear.
• In the phase 2 ATEMPT trial, researchers included 497 patients with stage I HER2-positive breast cancer, randomized 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab. Groups received either T-DM1 at 3.6 mg/kg once every 21 days for 17 cycles or paclitaxel 80 mg/m² plus trastuzumab 2 mg/kg intravenously weekly for 12 cycles, followed by trastuzumab 6 mg/kg every 21 days for an additional 13 cycles.
• The trial was powered for invasive disease-free survival with T-DM1 and for comparing toxicities. Recurrence-free interval and overall survival were also assessed.
• Correlative analyses included HER2DX genomic testing and multiomic evaluations of HER2 heterogeneity and predictors of recurrence and thrombocytopenia.

TAKEAWAY:

• In the final analysis at 5 years, the T-DM1 group had an invasive disease-free survival rate of 97.0% (with 11 invasive disease-free survival events and three distant recurrences), recurrence-free interval of 98.3%, overall survival of 97.8%, and breast cancer–specific survival of 99.4%.
• The researchers observed no difference in invasive disease-free survival with T-DM1 based on the tumor size, hazard ratio status, HER2 immunohistochemical score, and the receipt of T-DM1 for more or less than 6 months.
• Patients with high HER2DX risk scores had significantly higher risks for recurrence (invasive disease-free survival and recurrence-free interval), confirming prior findings.
• Rates of clinically relevant toxicities were similar between the T-DM1 and paclitaxel-trastuzumab groups, although patient-reported outcomes favored T-DM1, citing less alopecia and higher work productivity than that with paclitaxel plus trastuzumab.

IN PRACTICE:

“This final analysis of ATEMPT confirms the outstanding efficacy of T-DM1 at preventing recurrences of stage I HER2-positive breast cancer,” the authors concluded. “Overall, on the basis of the excellent long-term outcomes and favorable tolerability, 1 year of adjuvant T-DM1 represents an alternative treatment option to [paclitaxel plus trastuzumab] for patients with stage I HER2-positive breast cancer,” the authors added.

The results also provided additional data highlighting the “promise of HER2DX in tailoring treatment for early HER2-positive breast cancer,” the authors noted.

SOURCE:

The study, with first author Paolo Tarantino, MD, with Dana-Farber Cancer Institute, Boston, was published online on June 27 in the Journal of Clinical Oncology.

LIMITATIONS:

No germline genomic variants predictive of thrombocytopenia and bleeding with T-DM1 could be identified, possibly due to low statistical power or the complex, multifactorial mechanism of T-DM1–induced thrombocytopenia.

DISCLOSURES:

The study was funded by the American Society of Clinical Oncology. Tarantino has disclosed relationships (consulting/advisory) with Daiichi Sankyo/AstraZeneca, Lilly, Gilead Sciences, Genentech/Roche, and Novartis.