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.1

Recommended Dose/Route

  • The recommended dosage of T-DXd is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.1
T-DXd: Dose Reduction

T-DXd: Dose Reduction

Pivotal Study

  • DESTINY-Lung01 (NCT03505710)2, DESTINY-Lung02 (NCT04644237)3
  • Key Inclusion Criteria: Eligible patients were required to have unresectable or metastatic HER2-mutant non-squamous NSCLC with disease progression after one prior systemic therapy. Patients with a history of steroid dependent ILD/pneumonitis, clinically significant cardiac disease, clinically active brain metastases, and ECOG performance status >1 were excluded.1
  • Treatment: Assigned (2:1) to T-DXd 5.4 mg/kg or 6.4 mg/kg by intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.1
T-DXd: Efficacy Data

T-DXd: Efficacy Data

Safety and Adverse Event Management

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were nausea (61%), anemia (34%), fatigue (32%), constipation (31%), decreased appetite (30%), vomiting (26%), and alopecia (21%).1
  • Common Laboratory Abnormalities (≥20%): The most frequently reported laboratory abnormalities were decreased white blood cell count (60%), decreased hemoglobin (58%), decreased neutrophil count (52%), decreased lymphocyte count (43%), decreased platelet count (40%), decreased albumin (39%), increased aspartate aminotransferase (35%), increased alanine aminotransferase (34%), and increased alkaline phosphatase (22%).
  • Interstitial Lung Disease (ILD): 6%1
  • Dosage Interruption Due to Adverse Events (AEs): 23%1
  • Dosage Reductions Due to AEs: 11%1
  • Permanent Discontinuation Due to AEs: 8%1
T-DXd: Adverse Event Managment Strategies

T-DXd: Adverse Event Managment Strategies

References

1. ENHERTU (fam-trastuzumab deruxtecan-nxki). Prescribing information. Daiichi Sankyo Inc; February 2024. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true

2. Li BT, Smit EF, Goto Y, et al. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med.2022;386(3):241-251. doi:10.1056/NEJMoa2112431

3. Goto K, Goto Y, Kubo T, et al. Trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small-cell lung cancer: primary results from the randomized, phase II DESTINY-Lung02 Trial. J Clin Oncol. 2023;41(31):4852-4863. doi:10.1200/JCO.23.01361