4.7 Article

Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE

Journal

ANNALS OF ONCOLOGY
Volume 32, Issue 8, Pages 1005-1014

Publisher

ELSEVIER
DOI: 10.1016/j.annonc.2021.04.011

Keywords

adjuvant; residual invasive early breast cancer; HER2; peripheral neuropathy; thrombocytopenia

Categories

Funding

  1. F. Hoffmann-La Roche Ltd

Ask authors/readers for more resources

T-DM1 shows good safety and efficacy in patients with HER2-positive EBC, benefiting different subgroups without increasing the risk of central nervous system recurrence.
Background: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. Patients and methods: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/ axilla at surgery after NACT containing a taxane (+/- anthracycline, +/- platinum) and trastuzumab (+/- pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). Results: The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (w65% versusw82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the TDM1 arm (13.5% versus 3.8%), but there was no grade >3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.220.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. Conclusions: T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available