• With 6 months of additional follow-up, and more than half of the patients now with OS events T-DXd demonstrated an estimated median OS of 29.1 months and a high landmark survival at 12, 18, and 24 months (85%, 75%, and 58%, respectively)¹
  • There is a continuing increase in ORR and CR rates with the additional 6 months of follow-up
• These updated results continue to demonstrate a significant and sustained survival benefit of T-DXd in heavily previously treated patients with HER2 positive MBC (median prior lines of treatments, 6)¹
• Safety results were consistent with the known safety profile of T-DXd^2,3 
• T-DXd is currently undergoing further investigation in randomized controlled clinical trials assessing patients with:
  • HER2 positive BC (DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast05, DESTINY-Breast07, and DESTINY-Breast09)
  • HER2 low BC (DESTINY-Breast04 and DESTINY-Breast06)

BM Subgroup Analyses⁴: 

• T-DXd showed durable systemic disease control in patients with stable, treated BM at baseline, with clinical outcomes similar to those of the overall population (as of the August 1, 2019, DCO)
• Only 2.2% of patients (4 of 184) treated with T-DXd had progression in the brain including 2 patients with baseline BM
• Of 17 patients with brain lesions at baseline, 41.2% (n=7) experienced tumor shrinkage consistent with a PR in the brain and 41.2% (n=7) were consistent with SD
• Interpretation of these results is limited by the small patient number and post hoc analysis of CNS response

Biomarker analyses⁵:

• T-DXd treatment was associated with clinically significant ORR and durable responses across all patient subgroups
  • Clinical variables associated with better ORR, DOR, or median PFS in multivariate analyses included HER2 IHC 3+ status, pertuzumab given in the first or second line, fewer prior treatment regimens (continuous variable), and renal and hepatic function. All other variables tested did not significantly impact efficacy outcomes compared to the overall population
• Adjusted ERBB2 plasma copy number and HER2 ECD at baseline did not predict clinical outcomes in patients with HER2 positive BC
  • However, ERBB2 plasma copy number at cycle 4, day 1 was predictive for PFS and ORR and decreased in a majority of responders
• PIK3CA and ERBB2 GOF mutations detected in ctDNA at baseline were not associated with clinical outcomes
• Acquired gene alterations were observed in several genes