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 Mamounas, E. P., Untch, M., Mano, M. S., Huang, C., 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., Loibl, S. 2021


BACKGROUND: 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.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 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.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.

View details for DOI 10.1016/j.annonc.2021.04.011

View details for PubMedID 33932503