On August 11, 2022, fam-trastuzumab deruxtecan-nxki was granted accelerated approval for unresectable or metastatic non–small cell lung cancer (NSCLC) with tumors that have activating HER2 mutations, as detected by a U.S. Food and Drug Administration (FDA)-approved test and who have received a prior systemic therapy.1 The FDA also approved Life Technologies Corporation’s Oncomine Dx Target Test (tissue) and Guardant Health, Inc’s Guardant360 CDx (plasma) as companion diagnostics for trastuzumab deruxtecan.
Supporting Efficacy Data
Approval was based on an interim efficacy analysis in 52 patients (primary efficacy population) in the DESTINY-Lung02 trial (ClinicalTrials.gov identifier NCT04644237) who received the approved dose of 5.4 mg/kg every 3 weeks. Treatment continued until disease progression or unacceptable toxicity. An objective response on blinded independent central review was observed in 30 patients (58%, 95% confidence interval [CI] = 43%–71%), with a complete response in 1 (1.9%). The median duration of response was 8.7 months (95% CI = 7.1 months to not estimable).
How It Is Used
The recommended dose is 5.4 mg/kg 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.
Safety data are from 101 patients in the DESTINY-Lung02 trial who received trastuzumab deruxtecan at the approved dose. The most common adverse events of any grade (≥ 20%) were nausea, anemia, fatigue, constipation, decreased appetite, vomiting, and alopecia. The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (16%), decreased neutrophils (12%), and decreased hemoglobin (10%). Serious adverse events occurred in 30% of patients, with those occurring in > 1% of patients consisting of interstitial lung disease/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I.
Trastuzumab deruxtecan has boxed warnings for interstitial lung disease/pneumonitis and embryofetal toxicity. It also has warnings/precautions for neutropenia and left-ventricular dysfunction.
Fam-trastuzumab deruxtecan 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 fam-trastuzumab deruxtecan. For females and males of reproductive potential, pregnancy status of females should be verified prior to initiation of treatment.
1. Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use, prescribing information, Daiichi Sankyo, August 2022. www.accessdata.fda.gov/drugsatfda_docs/label/2022/761139s021lbl.pdf. Accessed August 30, 2022.