The Food and Drug Administration (FDA) has recently granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu). This approval is significant for adult patients suffering from unresectable or metastatic HER2-positive (IHC3+) solid tumors who have exhausted prior systemic treatment options. Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
Image Source: Vinoth Khandelwal
Enhertu was evaluated in three multicenter trials involving 192 adult patients with previously treated HER2-positive solid tumors. The trials demonstrated promising efficacy outcomes, with notable objective response rates (ORR) and durations of response (DOR). Patients enrolled in the trials received treatment until disease progression, death, or unacceptable toxicity. The major efficacy outcomes measured included ORR and DOR, assessed through independent central review. Notably, ORR ranged from 46.9% to 52.9%, with median DOR extending up to 19.4 months.
This approval marks a significant advancement in the management of HER2-positive solid tumors, providing a new option for patients who have exhausted standard treatments. The indication is tumor-agnostic, offering hope to a broader spectrum of patients facing this challenging condition.
The prescribing information highlights common adverse reactions and includes a Boxed Warning regarding risks of interstitial lung disease and embryo-fetal toxicity. The recommended dosage for this indication is 5.4 mg/kg administered intravenously every three weeks.
The accelerated approval of fam-trastuzumab deruxtecan-nxki represents a pivotal milestone in oncology, offering a targeted therapeutic option for patients with HER2-positive solid tumors. As part of Project Orbis, this approval signifies international collaboration in advancing cancer care. Continued evaluation in confirmatory trials will further elucidate the clinical benefits of this promising therapy.
Dr. Vinoth Khandelwal, Ph.D.
