Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE.
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO
oregon; portland; chiles; providence cancer institute
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 (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 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: 0.22-0.82), 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.
Earle A. Chiles Research Institute
Mamounas, E P; Untch, M; Mano, M S; Huang, C-S; Geyer, C E; von Minckwitz, G; Wolmark, N; Pivot, X; Kuemmel, S; DiGiovanna, M P; Kaufman, B; Kunz, G; Conlin, A K; Alcedo, J C; Kuehn, T; Wapnir, I; Fontana, A; Hackmann, J; Polikoff, J; Saghatchian, M; Brufsky, A; Yang, Y; Zimovjanova, M; Boulet, T; Liu, H; Tesarowski, D; Lam, L H; Song, C; Smitt, M; and Loibl, S, "Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE." (2021). Articles, Abstracts, and Reports. 5216.