FDA approves fam-trastuzumab deruxtecan-Nxki for unresectable or metastatic HER2-Positive Solid Tumors

By: Dr. Anish Shah
Bronx-Lebanon Hospital; Bronx, NY

On April 5, 2024, the Food and Drug Administration granted accelerated approval for
fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo, Inc.). The approval targets
adults with inoperable or metastatic HER2-positive (IHC3+) solid tumors who have previously undergone systemic treatment and lack satisfactory alternative treatment options.

The approval was based on the DESTINY-PanTumor02 (NCT04482309), DESTINY-
Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831) studies, all multicenter trials that included 192 adult patients with previously treated inoperable or metastatic HER2-positive (IHC 3+) solid tumors. The HER2 mutation was confirmed using an FDA approved HER2 test. Enhertu was given at a dosage of 5.4 mg/kg, delivered as an intravenous infusion once every three weeks (21-day cycle) until disease progression or unacceptable toxicity occurs. The median treatment duration varied across the studies.

Efficacy was established on objective response rate (ORR) and duration of response
(DOR), assessed by an independent central review according to RECIST v1.1. In
DESTINY-PanTumor02, the ORR stood at 51.4% (95% CI: 41.7, 61.0), with a median
DOR of 19.4 months. In DESTINY-Lung01, the ORR was 52.9% (95% CI: 27.8, 77.0), with a median DOR of 6.9 months. In DESTINY-CRC02, the ORR was 46.9% (95% CI: 34.3, 59.8), with a DOR of 5.5 months.

Common side effects of the medication included decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, fatigue, and others. A warning regarding the risk of interstitial lung disease and embryo-fetal toxicity is included in the prescribing information.

In summary, the FDA has fast-tracked approval for Enhertu for adults with inoperable or metastatic HER2-positive solid tumors. The recommended dosage is 5.4 mg/kg, delivered as an intravenous infusion once every three weeks until disease progression or unacceptable toxicity. This approval is based on the objective response rate and
duration of response and may require verification and description of clinical benefit in confirmatory trials for continued approval.