Abstract 96O
Background
In the phase 3 KATHERINE study (NCT01772472) adjuvant T-DM1 reduced the risk of invasive disease recurrence or death by 50% compared to adjuvant T in pts with residual invasive breast cancer after neoadjuvant chemotherapy plus HER2-targeted therapy. Here we present subgroup analyses: adjuvant radiotherapy (ART) vs no-ART; hormone receptor (HR)+ vs HR−/unknown disease; and HER2− status on retesting of a surgical specimen.
Methods
Pts were randomized to 14 q3w cycles of adjuvant T-DM1 (3.6 mg/kg) or T (6 mg/kg) with ART and hormonal therapy (HT) administered per local standards. Efficacy is reported according to tumor HR status; and safety according to HT received. The primary endpoint was invasive disease-free survival (IDFS). HER2 status was centrally assessed on available paired pre-neoadjuvant and surgical samples.
Results
Most pts received ART (82%) and/or HT (71%). IDFS benefit was consistent regardless of ART or HR status (Table). There were more grade ≥3 AEs (27.4% vs 16.2%) and serious AEs (13.2% vs 10.3%) with T-DM1 in the ART vs no-ART group. There were similar rates of grade ≥3 AEs (24.9% vs 26.0%) and serious AEs (12.2% vs 12.9%) with T-DM1 in the no-HT and HT groups. Of 845 pts with paired pre-neoadjuvant biopsy and surgical HER2 status data, 70 (8.3%) had residual disease which was considered HER2− (ie, HER2− or IHC 0-1+/ISH unk) on retesting. In this group, there have been no IDFS events among pts randomized to T-DM1 (n=28), and 11 events in pts randomized to T (n=42). Table: 96O
| 3-yr IDFS (95% CI) | Unstratified hazard ratio (95%CI) | |
| T ART | 77.4% (73.8–83.9) | 0.50 (0.38–0.66) |
| T-DM1 ART | 88.3% (85.5–91.0) | |
| T no-ART | 75.5% (67.6–83.5) | 0.50 (0.27–0.93) |
| T-DM1 no-ART | 88.2% (82.2–94.2) | |
| T HR+ | 80.7% (77.2–84.3) | 0.48 (0.35–0.67) |
| T-DM1 HR+ | 90.7% (88.1–93.4) | |
| T HR−/unknown | 66.6% (59.5–73.6) | 0.50 (0.33–0.74) |
| T-DM1 HR−/unknown | 82.1% (76.7–87.5) |
Conclusions
No new safety signals were observed with concomitant ART or HT. Exploratory HER2 analysis of paired specimens, suggests that T-DM1 should not be withheld in pts with HER2− residual disease at surgery. Thus HER2 retesting of residual disease may be unnecessary in this population.
Clinical trial identification
NCT01772472.
Editorial acknowledgement
Medical writing support, funded by F. Hoffmann–La Roche, was provided by Holly Strausbaugh, PhD,and Sheena Hunt, PhD, on behalf of Twist Medical.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
S. Loibl: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AbbVie; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: PriME/Medscape; Honoraria (self), Speaker Bureau/Expert testimony: Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Honoraria (institution), Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (institution), Speaker Bureau/Expert testimony: Lilly; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Samsung; Honoraria (institution), Advisory/Consultancy: Eirgenix. C-S. Huang: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): EirGenix; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo. M.S. Mano: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Lilly-Imlcone; Honoraria (self): Oncologia Brasil; Advisory/Consultancy: Amgen; Honoraria (self): DASA; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: AstraZeneca; Shareholder/Stockholder/Stock options: Biotoscana; Shareholder/Stockholder/Stock options: Hypera; Shareholder/Stockholder/Stock options: Fleury. T.P. Mamounas: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Exact Sciences (Genomic Health); Advisory/Consultancy: Merck; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Biotheranostics. C.E. Geyer: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Non-remunerated activity/ies, Medical writing and uncompensated advisory boards: Genentech/Roche; Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies, Uncompensated consulting and advisory board: Daiichi-Sankyo; Advisory/Consultancy, Travel/Accommodation/Expenses, Uncompensated advisory board: AstraZeneca; Advisory/Consultancy, Non-remunerated activity/ies, Uncompensated advisory board: Seattle Genetics; Non-remunerated activity/ies, Medical writing: AbbVie; Advisory/Consultancy, Non-remunerated activity/ies, Uncompensated consulting: Athenex. M. Untch: Advisory/Consultancy, all fees to the employer/institution: AbbVie; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: AstraZeneca; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Celgene; Advisory/Consultancy, all fees to the employer/institution: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Amgen; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Lilly; Advisory/Consultancy, all fees to the employer/institution: MSD Merck; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Mundipharma; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Myriad Genetics; Advisory/Consultancy, all fees to the employer/institution: Odonate; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Pfizer; Advisory/Consultancy, all fees to the employer/institution: Puma Biotechnology; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Roche Pharma; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Sanofi Aventis; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Novartis; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Pierre Fabre; Honoraria (institution), Advisory/Consultancy, all fees to the employer/institution: Clovis. G. von Minckwitz: Shareholder/Stockholder/Stock options: Cara GmbH. J-C. Thery: Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution), Travel/Accommodation/Expenses: Mundi Pharma; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: GSK. I. Schwaner: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: Hexal; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Servier. N. Loman: Honoraria (institution): Roche; Honoraria (institution): Pierre Fabre; Honoraria (institution): AstraZeneca; Honoraria (institution): MSD. K. Lübbe: Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. J.C. Chang: Advisory/Consultancy: Lilly USA; Advisory/Consultancy: Genentech; Advisory/Consultancy: Celgene. T. Hatschek: Honoraria (self), Advisory/Consultancy: Roche Sweden; Honoraria (self), Advisory/Consultancy: Pfizer Sweden; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Pfizer. D. Tesarowski: Full/Part-time employment: Genentech. T. Boulet: Full/Part-time employment: F. Hoffmann-La Roche. C. Wiese: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. C. Song: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. All other authors have declared no conflicts of interest.