In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus HER2-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant T-DM1 versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses.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).The incidence of peripheral neuropathy was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline peripheral neuropathy was associated with longer peripheral neuropathy 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 (HR=0.51; 95% 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 0.43-0.72). 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.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.
E P Mamounas, M Untch, M S Mano, C-S Huang, C E Geyer, G von Minckwitz, N Wolmark, X Pivot, S Kuemmel, M P DiGiovanna, B Kaufman, G Kunz, A K Conlin, J C Alcedo, T Kuehn, I Wapnir, A Fontana, J Hackmann, J Polikoff, M Saghatchian, A Brufsky, Y Yang, M Zimovjanova, T Boulet, H Liu, D Tesarowski, L H Lam, C Song, M Smitt, S Loibl