Abstract CT096: Trastuzumab emtansine (T-DM1) + capecitabine in HER2-positive metastatic breast cancer (mBC) and HER2-positive locally advanced (LA)/metastatic gastric cancer (mGC): Results from the phase I/randomized phase II TRAXHER2 study
Authors: Cortes Javier , Dieras Véronique , Lorenzen Sylvie , Montemurro Filippo , Riera-Knorrenschild Jorge , Thuss-Patience Peter , Allegrini Giacomo , Laurentiis Michele De , Lichinitser Mikhail , Lohrisch Caroline , Perez-Garcia Jose , Ricci Francesco , Sakaeva Dina , Serpanchy Rosanne , Sufliarsky Jozef , Vidal Maria , Irahara Natsumi , Wohlfarth Christine , Aout Mounir , Gelmon Karen 
Published: August 2018

Abstract
TRAXHER2 is a phase 1 dose-finding study in mBC and LA/mGC followed by a randomized, international, multicenter phase 2 study of efficacy and safety of T-DM1 + capecitabine in pts with human epidermal growth factor receptor 2 (HER2)-positive mBC. Rationale for this combination is supported by preclinical data demonstrating an additive effect.
Phase 1 assessed maximum tolerated doses (MTDs) for mBC and mGC using a 3+3 design, with dose modification of capecitabine. The MTD for mBC based on 11 dose limiting toxicity (DLT)-evaluable pts was capecitabine 700 mg/m2 BID (days 1-14 of 3-wk cycle) + T-DM1 3.6 mg/kg Q3W. The starting phase 1 capecitabine mGC dose was based on the mBC MTD. For mGC, the MTD based on 6 DLT-evaluable pts was capecitabine 700 mg/m2 BID (days 1-14 of 3-wk cycle) + T-DM1 2.4 mg/kg QW.
In phase 2 mBC pts were randomized to T-DM1 (3.6 mg/kg Q3W) + capecitabine (at the MTD from phase 1) or T-DM1 alone. The primary outcome was investigator-assessed overall response rate (ORR). Secondary end points included safety and progression-free survival (PFS).
161 mBC pts (median age 52 yrs; range 28-80 yrs) were randomized to T-DM1 + capecitabine (n=81) or T-DM1 alone (n=80). Most pts were Caucasian, female, had a performance status of 0-1, had visceral disease, and received ≤1 prior mBC treatments.
There was no statistically significant difference in ORR between pts who received T-DM1 + capecitabine vs T-DM1 alone (44.4% vs 36.3%; P=0.336). Efficacy and safety results are shown (Table). The safety profile was consistent with previous reports. In both arms, most pts had an adverse event (AE); the incidences of AEs (95% vs 88%) and grade 3/4 AEs (44% vs 41%) were numerically higher with the combination. No Grade 5 AEs occurred.
In conclusion, the addition of capecitabine to T-DM1 does not enhance anti-tumor efficacy in pts with HER2-positive mBC.
T-DM1 + capecitabineT-DM1Efficacy, n8180ORR, n (%)36 (44.4) 90% confidence interval (CI), 35.0, 54.229 (36.3) 90% CI, 27.3, 46.0Difference8.2% (90% CI, −4.5, 20.9) P=0.336Clinical benefit rate, n (%)154 (66.7)50 (62.5)Responders, n (%)Complete response2 (2.5)2 (2.5)Partial response34 (42.0)27 (33.8)Stable disease24 (29.6)26 (32.5)Progressive disease14 (17.3)23 (28.8)Not evaluable7 (8.6)2 (2.5)Median PFS, months10.29.8Safety, n8278Any AE, n (%)78 (95.1)69 (88.5)Thrombocytopenia35 (42.7)21 (26.9)Nausea27 (32.9)18 (23.1)Increased aspartate aminotransferase27 (32.9)31 (39.7)Increased alanine aminotransferase20 (24.4)24 (30.8)Grade 3 AEs36 (43.9)30 (38.5)Grade 4 AEs3 (3.7)3 (3.8)Treatment-related AEs72 (87.8)60 (76.9)Serious AEs11 (13.4)10 (12.8) 1Complete response + partial response + stable disease for &gt;6 months. Citation Format: Javier Cortes, Véronique Dieras, Sylvie Lorenzen, Filippo Montemurro, Jorge Riera-Knorrenschild, Peter Thuss-Patience, Giacomo Allegrini, Michele De Laurentiis, Mikhail Lichinitser, Caroline Lohrisch, Jose Perez-Garcia, Francesco Ricci, Dina Sakaeva, Rosanne Serpanchy, Jozef Sufliarsky, Maria Vidal, Natsumi Irahara, Christine Wohlfarth, Mounir Aout, Karen Gelmon. Trastuzumab emtansine (T-DM1) + capecitabine in HER2-positive metastatic breast cancer (mBC) and HER2-positive locally advanced (LA)/metastatic gastric cancer (mGC): Results from the phase I/randomized phase II TRAXHER2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT096.