Background
Trastuzumab deruxtecan (T-DXd; DS-8201) is an antibody-drug conjugate with an anti-HER2 antibody, a peptide-based cleavable linker, and a novel topoisomerase I inhibitor payload. T-DXd demonstrated antitumor activity and manageable safety in HER2-expressing/mutated solid tumors.

Methods
The pooled analysis of the overall population and Japanese patients (pts) from the first-in-human Ph1 study (J101 study; NCT02564900) and an open-label, international, multicenter, Ph2 study (DESTINY-Breast01; NCT03248492) of T-DXd in pts with HER2+ metastatic BC were conducted.

Results
Among 545 pts enrolled in 2 studies, 235 were HER2+BC pts and enrolled at Recommended Phase II Dose (RP2D, 5.4 mg/kg). Median number of prior treatment regimens was 6 (range, 2-27) including pertuzumab (70%). At data cutoff (Ph1: Feb 1, 2019; Ph2: Mar 21, 2019), 120 pts (51%) remained on T-DXd treatment (median duration of treatment: 7.0 months).
The confirmed ORR by independent central review in pts treated at the RP2D was 58% (95% CI, 52, 65) in overall pooled population. ORRs were consistent across subgroups, including those with prior pertuzumab and those with ≧3 prior regimens. Preliminary median duration of response and PFS were 16.9 and 13.9 months, respectively. In Japanese population (n=51), ORR was 65% (95% CI, 50, 78).
TEAEs occurred in all 235 pts (grade≧3, 50%); most common grade≧3 AEs were decreased neutrophil count (16%), nausea (7%), anemia (7%), and fatigue (5%). 22 pts (9%) had interstitial lung disease (ILD) related to T-DXd judged by an independent adjudication committee; 10 pts (20%) were Japanese and none of the 10 had grade≧3 ILDs. Safety data in Japanese subset will be presented.

Conclusion
T-DXd 5.4 mg/kg treatment demonstrated clinically meaningful activity in extensively pretreated HER2+ metastatic BC pts including Japanese pts. T-DXd had a generally manageable safety profile, with ILD identified as a risk warranting proactive awareness and management.