On April 5, 2024, fam-trastuzumab deruxtecan-nxki (T-DXd) was granted accelerated approval for adults with unresectable or metastatic HER2-positive (immunohistochemistry 3+) solid tumors who received prior systemic treatment and have no satisfactory alternative treatment options.¹

Supporting Efficacy Data

Approval was supported by findings in 192 patients from three multicenter trials: DESTINY-PanTumor02 (ClinicalTrials.gov identifier NCT04482309; n = 111), DESTINY-Lung01 (NCT03505710; n = 17), and DESTINY-CRC02 (NCT04744831; n = 64), in which participants received T-DXd at 5.4 mg/kg every 3 weeks. All trials excluded patients with a history of interstitial lung disease/pneumonitis requiring treatment with steroids or interstitial lung disease/pneumonitis at screening, clinically significant cardiac disease, and active brain metastases. The most common tumor types were colorectal (n = 64), bladder (n = 27), and biliary tract (n = 22).

In DESTINY-PanTumor02, an objective response was observed in 51.4% (95% CI = 41.7%–61.0%) of patients, and the median response duration was 19.4 months (range = 1.3 months to 27.9+ months). In DESTINY-Lung01, the objective response rate was 52.9% (95% CI = 27.8%–77.0%), and the median response duration was 6.9 months (range = 4.0 months to 11.7+ months). In DESTINY-CRC02, the objective response rate was 46.9% (95% CI = 34.3%–59.8%), and the median response duration was 5.5 months (range = 1.3+ months to 9.7+ months).

How It Is Used

The recommended dosage of T-DXd is 5.4 mg/kg given via intravenous infusion once every 3 weeks until disease progression or unacceptable toxicity. Product labeling provides instructions on dosage modification, including dose reduction, for adverse reactions including interstitial lung disease/pneumonitis, neutropenia, febrile neutropenia, thrombocytopenia, and left ventricular dysfunction.

Safety Profile

Among 347 patients in DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02, and DESTINY-Breast01 who received T-DXd, the most common adverse events of any grade were nausea (69%), fatigue (59%), vomiting (35%), decreased appetite (34%), alopecia (34%), and diarrhea (31%). The most common grade 3 or 4 adverse events included fatigue (10%), nausea (7%), and diarrhea (4.3%). The most common grade 3 or 4 laboratory abnormalities were decreased neutrophils (21%), lymphocytes (21%), white blood cells (11%), and hemoglobin (10%).

Serious adverse events occurred in 34% of patients, most commonly (> 1%) sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19 infection, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea. Treatment was discontinued because of adverse events in 15% of patients, most commonly interstitial lung disease/pneumonitis (10%). Adverse events led to death in 6.3% of patients, including interstitial lung disease/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 infection (0.6%), and sepsis (0.6%).

T-DXd has boxed warnings for interstitial lung disease/pneumonitis and embryofetal toxicity. It also has warnings/precautions for neutropenia and left ventricular dysfunction. Patients should be advised not to breastfeed while receiving T-DXd. For females and males of reproductive potential, pregnancy status of females should be verified prior to initiation of treatment. 

REFERENCE

1. Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use, prescribing information, Daiichi Sankyo Co, Ltd, April 2024. Available at https://www.enhertu.com. Accessed April 17, 2024.