Initial US Approval

20191

Indications

  • The treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen.1
  • The treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.1
  • The treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.*1
  • The treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ ISH positive) gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.1
  • The treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.*1

*These indications are approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Recommended Dose/Route

  • The recommended dosage of T-DXd in HER2+ metastatic gastric cancer is 6.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.1
Dose Reductions for Adverse Events with T-DXd

Dose Reductions for Adverse Events with T-DXd

Pivotal Studies

  • DESTINY-Gastric01 (NCT03329690)2,3
  • Key Inclusion Criteria: Patients with HER2-positive (IHC 3+ or IHC 2+/ISH-positive), locally advanced or metastatic gastric or GEJ adenocarcinoma who had progressed on at least 2 prior regimens including trastuzumab, a fluoropyrimidine- and a platinum-containing chemotherapy.1
  • Treatment: Patients were randomly assigned 2:1 to receive T-DXd, 6.4 mg/kg, intravenously every 3 weeks or physician’s choice of chemotherapy: irinotecan monotherapy, 150 mg/m2, intravenously every 2 weeks or paclitaxel monotherapy, 80 mg/m2, intravenously weekly.1
T-DXd: Efficacy Data

T-DXd: Efficacy Data

Safety

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were nausea (63%), decreased appetite (60%), anemia (58%), fatigue (55%), diarrhea (32%), vomiting (26%), constipation (24%), pyrexia (24%), and alopecia (22%).1
  • Common Laboratory Abnormalities (≥20%): The most frequently reported laboratory abnormalities were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), increased aspartate aminotransferase (58%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), and increased blood bilirubin (24%).1
  • Dosage Interruption due to Adverse Events (AEs): 62%1
  • Dosage Reductions due to AEs: 32%1
  • Permanent Discontinuation due to AEs:15%1

References

  1. ENHERTU (fam-trastuzumab deruxtecan-nxki). Prescribing information. Basking Ridge, NJ, USA: Daiichi Sankyo, Inc., 02/2024. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true
  2. Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382(25):2419-2430. doi: 10.1056/NEJMoa2004413.
  3. Yamaguchi K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: final overall survival (OS) results from a randomized, multicerter, open-label, phase 2 study (DESTINY-Gastric01). J Clin Oncol. 2022;40(4supp):242. doi: 10.1200/JCO.2022.40.4_suppl.24.