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-PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831)2,3,4
Summary of Pivotal Studies

Summary of Pivotal Studies

T-DXd: Efficacy Data

T-DXd: Efficacy Data

Safety and Adverse Event (AE) Management

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were nausea (69%), fatigue (59%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), constipation (28%), stomatitis (20%), and upper respiratory tract infection (20%).1
  • Common Laboratory Abnormalities (≥20%): The most frequently reported laboratory abnormalities were decreased white blood cell count (75%), decreased hemoglobin (67%), decreased neutrophil count (66%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), decreased blood potassium (29%), and decreased sodium (22%).1
  • Interstitial Lung disease (ILD): ILD was reported in 16% of patients and accounted for treatment discontinuation in 10% of patients.1
  • Dosage Interruptions Due to Adverse Events (AEs): 48%1
  • Dose Reductions Due to AEs: 27%1
  • Permanent Discontinuation Due to AEs: 15%1
T-DXd: Most Common Adverse Events of Grade 3 or 4

T-DXd: Most Common Adverse Events of Grade 3 or 4

T-DXd: Adverse Event Management Strategies

T-DXd: Adverse Event Management Strategies

References

  1. ENHERTU (fam-trastuzumab deruxtecan-nxki). Prescribing information. Daiichi Sankyo; 2024. Accessed October 4, 2024. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true
  2. Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol. 2024;42(1):47-58. doi:10.1200/JCO.23.02005
  3. Smit EF, Felip E, Uprety D, et al. Trastuzumab deruxtecan in patients with metastatic non-small-cell lung cancer (DESTINY-Lung01): primary results of the HER2-overexpressing cohorts from a single-arm, phase 2 trial. Lancet Oncol. 2024;25(4):439-454. doi:10.1016/S1470-2045(24)00064-0
  4. Yoshino T, Di Bartolomeo M, Raghav K, et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun. 2023;14(1):3332. doi:10.1038/s41467-023-38032-4
  5. Tarantino P, Tolaney SM. Detecting and managing t-dxd-related interstitial lung disease: the five “s” rules. JCO Oncol Pract. 2023;19(8):526-527. doi:10.1200/OP.23.00097
  6. NCCN. Clinical Practice Guidelines in Oncology. Antiemesis, version 2.2024. Accessed October 7, 2024. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf