1O Trastuzumab emtansine (T-DM1) vs trastuzumab (H) in Chinese patients (pts) with residual invasive disease after neoadjuvant chemotherapy for HER2-positive breast cancer (BC) in the phase III KATHERINE study

Background Pts with HER2+ early BC and residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy have a higher risk of recurrence and death than those with a pCR. The KATHERINE (NCT01772472) study showed significantly improved invasive disease-free survival (IDFS) with adjuvant T-DM1 vs H in this population. Here, we compare Chinese pts in KATHERINE to the overall population. Methods Pts with HER2+ BC and residual invasive disease after taxane- and H-containing neoadjuvant chemotherapy followed by surgery were randomized 1:1 to 14 cycles of adjuvant T-DM1 (3.6 mg/kg IV q3w) or H (6 mg/kg IV q3w). IDFS and the secondary endpoints of disease-free survival including non-invasive breast cancers, overall survival, distant recurrence-free interval, and safety were compared between Chinese pts (mainland China, Taiwan, Hong Kong) and the overall population. Results There were 101 (6.8%) Chinese pts in KATHERINE. IDFS was greater in the T-DM1 vs the H group (HR = 0.57; 95% CI: 0.25–1.31), with similar results for secondary endpoints (Table). As in the overall population, Chinese pts receiving T-DM1 vs H had more grade ≥3 adverse events (AEs; 39% vs 4%), serious AEs (SAEs; 20% vs 2%); and AEs leading to treatment discontinuation (28% vs 0). The most common grade ≥3 AE in the T-DM1 arm was thrombocytopenia (22%), a frequency higher than in the overall population (6%). Grade ≥3 hemorrhage was reported in 1 pt (T-DM1 arm). All grade ≥3 thrombocytopenia was resolved or resolving at data cutoff. Table 1O Table Chinese Overall H T-DM1 H T-DM1 (N = 50) (N = 51) (N = 743) (N = 743) IDFS Pts with event, n (%) 14 (28.0) 9 (17.6) 165 (22.2) 91 (12.2) 3-yr EF rate, % 70.4 83.8 77.0 88.3 HR a (95% CI) 0.57 (0.25–1.31) 0.50 (0.39–0.64); P < 0.001 DFS Pts with event, n (%) 14 (28.0) 9 (17.6) 167 (22.5) 98 (13.2) 3-yr EF rate, % 70.4 83.8 76.9 87.4 HR a (95% CI) 0.57 (0.25–1.31) 0.53 (0.41–0.68) OS Pts with event, n (%) 4 (8.0) 3 (5.9) 56 (7.5) 42 (5.7) 5-yr EF rate, % 90.2 93.6 86.8 92.1 HR a (95% CI) 0.68 (0.15–3.04) 0.70 (0.47–1.05) DRFI Pts with event, n (%) 8 (16.0) 6 (11.8) 121 (16.3) 78 (10.5) 3-yr EF rate, % 82.3 89.5 83.0 89.7 HR a (95% CI) 0.68 (0.24–1.97) 0.60 (0.45–0.79) a unstratified hazard ratio Abbreviations: EF, event-free; IDFS, invasive disease-free survival; DFS, disease-free survival (including noninvasive breast cancers); OS, overall survival; DRFI, distant recurrence-free interval. Conclusions Consistent with the overall study population, T-DM1 was associated with increased efficacy compared to H in Chinese pts. Compared to all pts, increases in SAEs, grade ≥3 AEs, and AEs leading to discontinuation were observed in Chinese pts and were driven by an increase in thrombocytopenia, consistent with previous data in Asian pts. Clinical trial identification NCT01772472. Editorial acknowledgement Medical writing assistance was provided by Twist Medical and was funded by F. Hoffmann–La Roche. Legal entity responsible for the study F. Hoffmann-La Roche. Funding F. Hoffmann-La Roche. Disclosure C. Huang: 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; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): EirGenix; Research grant / Funding (institution): MSD; Research grant / Funding (institution): OBI Pharma. Y. Yang: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Ono; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Mundipharma; Research grant / Funding (institution): Orient Europharma; Full / Part-time employment: Taichung Veterans General Hospital. A. Kwong: Honoraria (self), ICG Fluorescence in Breast Surgery speaker: Stryker; Honoraria (self), Chairing Meeting: AstraZeneca; Honoraria (self), Chairing Meeting: Pfizer; Honoraria (self), Honoraria (institution), Chairing Meeting, Support on trial to HKU: Roche; Honoraria (institution), Suppprt on trial to HKU: Merck; Honoraria (institution), Support on trial to HKU: Novartis; Honoraria (institution), Supporting device & consumables for Prospective Study on Cryosurgery for treatment of Early Breast Cancer.: WKK Medical Equipment company limited; Leadership role, Chairman: Hong Kong Hereditary Breast Cancer Family Registry; Leadership role, Founding member: Asian BRCA (ABRCA); Leadership role, Council Member: Hong Kong Society of Breast Surgeons. L-M. Tseng: Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: AstraZeneca. M-C. Liu: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche. Y. Feng: Full / Part-time employment: Roche (China) Holding Ltd. G. Sun: Full / Part-time employment: Roche (China) Holding Ltd. I.R. Yan: Full / Part-time employment: Roche (China) Holding Ltd. All other authors have declared no conflicts of interest.