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

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.

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure EPM reports consulting fees from Biotheranostics, Daiichi Sankyo, Genentech/Roche, Genomic Health, Merck, and Puma Biotechnology, and speaker bureau fees from Genentech and Genomic Health. MU reports consulting fees from the following companies, which have been paid to his institution: AbbVie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly Germany, Lilly International, Merck, MSD Mundipharma, Myriad Genetics, Novartis, Odonate, Pierre Fabre, Pfizer, Puma Biotechnology, F. Hoffmann-La Roche, Sanofi Aventis, and TEVA Pharmaceuticals. MSM reports honoraria for advisory boards and presentations in educational events from AstraZeneca, Lilly, MSD, Novartis, Oncologia Brasil, Pfizer, and Roche; educational support from Novartis, Pfizer, and Roche; and stock ownership in Biotoscana, Hypera Pharma, and Fleury. C-SH reports consulting fees from Amgen, Lilly, Novartis, Pfizer, and Roche; contracted research from AstraZeneca, Eirgenix, Lilly, MSD, Novartis, OBI, Pfizer, and Roche; travel expenses from Amgen, Pfizer, and Roche; and he serves on speakers bureaus for Pfizer and Roche. CEG reports consulting fees from Athenex, Celgene, Exact Science, Myriad Genetics, and Heron; uncompensated consulting for Daiichi Sankyo, Genentech, Roche, and Seattle Genetics; travel expenses from AstraZeneca, Daiichi Sankyo, and Roche; and medical writing support from AbbVie and Roche. GvM reports consulting fees from Amgen and Roche; contracted research from AbbVie, Amgen, AstraZeneca, Celgene, Myriad Genetics, Pfizer, Roche, and Vifor Pharma; and stock ownership in Cara GmbH (ARO). SK reports consulting fees from Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD Oncology, Novartis, Pfizer, Puma Biotechnology, PFM Medical, Roche, and SOMATEX; and travel expenses from Daiichi Sankyo and Roche. MPDG reports royalties from DAKO and Neomarkers; consulting fees from Merck; and serves on a speaker’s bureau for Total Health Conferencing. BK reports speaker fees and honoraria from Roche; and has served on advisory boards for AstraZeneca, Novartis, Pfizer, and Roche. GK reports honoraria for advisory boards and presentations in educational events from Roche. TK reports honoraria from Celgene, Pfizer, and Roche. IW reports consulting fees from Cardinal Health and Vector Science; and contracted research with Lumicell, NOVADAQ, OncoSec, and Roche. MS reports consulting fees from Eisai, Lilly, MSD, Novartis, Pfizer, Roche, and Sandoz; and contracted research from AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pfizer, Roche, and Sandoz. AB reports consulting fees from Agendia, Bayer, Bioarray Therapeutics, Biotheranostics, Celgene, Eisai, Genentech, Genomic Health, Lilly, Merck, Myriad Pharmaceuticals, NanoString Technologies, Novartis, Pfizer, Puma Biotechnology, and Roche. YY reports research funding paid to his institution from Astellas, Celgene, Janssen, Lilly, Mundipharma, Novartis, Ono, Orient EuroPharma, and Roche. SL reports research funding and/or honoraria from the following companies which have been paid to her institution: AbbVie, Amgen, AstraZeneca, Celgene, Celltrion, Cepheid, Daiichi Sankyo, EirGenix, E-vate, Roche, GH, Immunomedics, Ipsen, Medscape, Myriad Pharmaceuticals, Novartis, PEER, Pfizer, Pierre Fabre, prIME, Puma Biotechnology, SeaGen, Sividon Diagnostics, TEVA Pharmaceuticals, and Vifor. TB is an employee of Parexel International GmbH, contracted by F. Hoffmann-La Roche Ltd, during the conduct of the study. HL, DT, LHL, and CS are employees of Genentech and hold stock in Roche. MS was an employee of Genentech during the conduct of the study. All other authors have declared no conflicts of interest.