4667 - Peripheral neuropathy (PN), thrombocytopenia (TCP) and central nervous system (CNS) recurrence: an update of the phase III KATHERINE trial of post-neoadjuvant trastuzumab emtansine (T-DM1) or trastuzumab (H) in patients (pts) with residual invasive HER2-positive breast cancer (BC)

Background

We analyzed KATHERINE trial (NCT01772472) data to assess TCP, PN and CNS recurrence, key considerations in anti-HER2 treatment of BC pts.

Methods

Pts received 14 cycles of post-neoadjuvant T-DM1 (3.6 mg/kg IV q3w) or H (6 mg/kg IV q3w). Safety (per NCI CTCAE v4.0; all pts receiving ≥1 dose of study drug) and CNS recurrence (intent-to-treat population) were assessed.

Results

Baseline (BL) neuropathy was well balanced between arms (T-DM1 22.7%; H 21.4%). In both arms, BL neuropathy was not associated with higher PN incidence (T-DM1 36.3% H 17.5% vs T-DM1 31.1% H 16.8%) however it was associated with longer median PN duration and lower resolution rate (352–337 days [d] 66–64% vs 243–232 d 81–83%). PN incidence was similar, irrespective of prior taxane (docetaxel T-DM1 32%; H 18%; paclitaxel T-DM1 32%; H 17%). In the T-DM1 arm, prior platinum was associated with higher TCP incidence (mostly grade 1–2) (36% vs 27%) while median duration and resolution rate of grade 3–4 TCP were similar regardless of prior platinum (33 d vs 29 d; 95% vs 96%). In the H arm, TCP rate was only 2.4% precluding further analysis. The numerically higher rate of CNS recurrence as first IDFS event for T-DM1 may be explained by competing risk, as observed in H adjuvant trials. T-DM1 was not associated with an increased overall risk of CNS recurrence and there was no evidence of subsequent overall survival (OS) detriment (Table).Table: LBA19

CNS recurrence analysis

Conclusions

BL neuropathy may impact duration and resolution of PN with T-DM1 or H, but PN incidence was not affected by BL neuropathy or type of prior taxane. Prior platinum was associated with higher TCP incidence in the T-DM1 arm. The numerical difference in CNS recurrence as first IDFS event for T-DM1 vs H may be explained by competing risk and had no detrimental effect on OS.

Clinical trial identification

NCT01772472.

Editorial acknowledgement

Medical writing support was provided by Ify Sargeant of Twist Medical LLC and funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffmann-La Roche.

Funding

F. Hoffmann-La Roche.

Disclosure

M. Untch: Honoraria (institution), Non-remunerated activity/ies: AbbVie; Honoraria (institution), Non-remunerated activity/ies: Amgen GmbH; Honoraria (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (institution), Non-remunerated activity/ies: BMS; Honoraria (institution), Non-remunerated activity/ies: Celgene GmbH; Honoraria (institution), Non-remunerated activity/ies: Daiji Sankyo; Honoraria (institution), Non-remunerated activity/ies: Eisai GmbH; Honoraria (institution), Non-remunerated activity/ies: Janssen Cilag/ J&J; Honoraria (institution), Non-remunerated activity/ies: Lilly Deutschland/ Lilly Int.; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ies: Myriad Genentics; Honoraria (self), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies: Riemser; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies: Sividon Diagnostics; Honoraria (institution), Non-remunerated activity/ies, Same disclosures for Novartis: TEVA Pharmaceuticals Ind Ltd. C.E. Geyer: Research grant / Funding (institution), Travel / Accommodation / Expenses, Medical writing support, travel/hotel expenses for non-compensated advisory board attendance: Genentech/Roche; Travel / Accommodation / Expenses, Travel/hotel expenses for Steering Committee activities: AstraZeneca; Non-remunerated activity/ies, Non-financial support, medical writing support : AbbVie; Advisory / Consultancy, Advisory Board: Celgene. C. Huang: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: Novartis; Honoraria (self): EirGenix; Honoraria (self): OBI Pharma; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Daiichi Sankyo. S. Loibl: Honoraria (institution): Roche; Honoraria (institution): AbbVie; Honoraria (institution): Amgen; Honoraria (institution): AstraZeneca; Honoraria (institution): Celgene; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Seattle Genetics; Honoraria (institution): Teva; Honoraria (institution): Vifor; Honoraria (institution): PRIME; Honoraria (institution): Daiichi; Licensing / Royalties: EP14153692.0 pending. M.S. Mano: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Oncologica Brasil; Honoraria (self), Advisory / Consultancy: AstraZeneca; Shareholder / Stockholder / Stock options: Hypera; Shareholder / Stockholder / Stock options: Fleury; Shareholder / Stockholder / Stock options: Biotoscana. G. von Minckwitz: Honoraria (institution): Pfizer; Honoraria (self), Honoraria (institution): Amgen; Honoraria (self), Honoraria (institution): Roche; Honoraria (institution): Celgene; Honoraria (institution): AstraZeneca; Honoraria (institution): Myriad Genetics; Honoraria (institution): AbbVie; Honoraria (self): Vifor Pharma. A. Brufsky: Advisory / Consultancy: Eisai; Advisory / Consultancy: Myriad Pharmaceuticals; Advisory / Consultancy: Merck; Advisory / Consultancy: Bioarray Therapeutics; Advisory / Consultancy: Puma Biotechnology; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: NanoString Technologies; Advisory / Consultancy: BioTheranostics; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bayer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Celgene; Advisory / Consultancy: Agendia; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Pfizer. B. Kaufman: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy: AZ; Advisory / Consultancy: Novartis. T. Boulet: Research grant / Funding (institution): Genentech. H. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. C. Song: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. E.P. Mamounas: Honoraria (self): Genentech/Roche; Honoraria (self): Genomic Health, Inc.; Honoraria (self): Biotheranostics; Honoraria (self): Merck; Honoraria (self): Daiichi Sankyo. All other authors have declared no conflicts of interest.