Article

Trastuzumab Deruxtecan Demonstrates Efficacy in Metastatic Breast Cancer

Trastuzumab deruxtecan (T-DXd) (Enhertu) demonstrated strong efficacy in a phase 2 trial for treatment of HER2-positive metastatic breast cancer.

Trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) demonstrated strong efficacy in a phase 2 trial for treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). The DESTINY-Breast01 trial showed an effective response rate of 60.9% and median progression-free survival (mPFS) of 16.4 months, according to researchers.1

Results of the study, funded by Daiichi Sankyo, were presented in a poster session during the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, May 29-31.1

HER2 is overexpressed in approximately 15% to 20% of metastatic breast cancers.1 T-DXd is a HER2-directed antibody-drug conjugate, comprised of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload by a tetrapeptide-based linker.2

The trial, DESTINY-Breast01, was a single-group, open-label, multicenter, study of 184 participating patients who received T-DXd at 5.4 mg/kg. These were patients with HER2-positive mBC who were previously treated with trastuzumab emtansine (T-DM1) and had an Eastern Cooperative Oncology Group performance status of 0 or 1.1

Multivariate analysis using logistic regression models (ORR) and Cox proportional hazards models (duration of response [DOR], mPFS) explored 15 relevant clinical predictor variables. Circulating tumor DNA (ctDNA) was collected prior to the first dose, every 3 cycles of treatment, and at the end of treatment. Sequencing for single-nucleotide variation/insertion and deletion, amplification, and fusion of ≈ 500 genes was done.1

Efficacy in all evaluated clinical subgroups was similar to the overall response rate (ORR) of 60.9% (112/184; 95% CI, 53.4%-68.0%) and mPFS of 16.4 months (95% CI, 12.7 months to not reached) with ranges from ORR 46.4%-74.5%, and mPFS 12.3-18.1 months. The median DOR was 14.8 months (95% CI, 13.8-16.9 months).1

Variables associated with improved ORR, DOR, or mPFS included hormone receptor positive status, fewer prior treatment regimens, pertuzumab given in the first or second line, and normal renal and hepatic function. Variables that did not impact efficacy outcomes compared with the overall population include age, race, region, ECOG PS, HER2 IHC 3+ status, progesterone receptor status, best response to T-DM1, time since diagnosis, and history of brain metastases.1

Metastases were most commonly observed in the liver, lung, and lymph nodes in 48 patients with progression as of data cut date. Only 8% of these 48 patients had progression involvement in the brain upon disease progression. Decrease of ERBB2 copy number in ctDNA was seen on treatment and correlated with clinical response. Additional changes in molecular markers on treatment and following progression will be described.1

Officials with the FDA approved TDX-d in December 2019 for the treatment of adults with unresectable or metastatic HER2-positive breast cancer that have received 2 or more prior anti-HER2-based regimens in the metastatic setting.3

REFERENCES

  • Modi S, Andre F, Krop I, et al. Trastuzumab deruxtecan for HER2-positive metastatic breast cancer: DESTINY-Breast01 subgroup analysis. Presented at: 2020 ASCO Virtual Scientific Program, May 29-31, 2020.
  • Daiichi Sankyo Launches ENHERTU® in Japan for Patients with HER2-Positive Unresectable or Metastatic Breast Cancer [news release]. Tokyo, Munich and Basking Ridge, NJ; May 25, 2020: Daiichi-Sankyo. https://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/007137.html Accessed June 1, 2020.
  • Murphy J. New Treatment Option for Certain Patients with HER2-Positive Breast Cancer Granted FDA Approval. Pharmacy Times™. https://www.pharmacytimes.com/news/new-treatment-option-for-certain-patients-with-her2-positive-breast-cancer-granted-fda-approval Published December 20, 2019. Accessed June 1, 2020.

Related Videos
Hands holding a crochet heart | Image Credit: © StockerThings - stock.adobe.com
Wooden blocks spelling HDL, LDL | Image Credit: © surasak - stock.adobe.com
Anticoagulant attacking blood clot | Image Credit: © BURIN93 - stock.adobe.com
Depiction of man aging | Image Credit: © Top AI images - stock.adobe.com
Map with pins | Image Credit: © Tryfonov - stock.adobe.com
Heart with stethoscope | Image Credit: © DARIKA - stock.adobe.com
Image Credit: © abricotine - stock.adobe.com