96O Adjuvant trastuzumab emtansine (T-DM1) vs trastuzumab (T) in patients (pts) with residual invasive disease after neoadjuvant therapy for HER2+ breast cancer: Subgroup analysis from KATHERINE

Abstract

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. 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. 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).Table3-yr IDFS (95% CI)Unstratified hazard ratio (95%CI)T ART77.4% (73.8–83.9)0.50 (0.38–0.66)T-DM1 ART88.3% (85.5–91.0)T no-ART75.5% (67.6–83.5)0.50 (0.27–0.93)T-DM1 no-ART88.2% (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−/unknown66.6% (59.5–73.6)0.50 (0.33–0.74)T-DM1 HR−/unknown82.1% (76.7–87.5) Open table in a new tab 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.