Enhertu: The first drug approved for HER2-mutant NSCLC
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On August 11, 2022, the FDA gave the green light for accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) to treat adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The following approval makes fam-trastuzumab deruxtecan-nxki the first drug approved for HER2-mutant NSCLC.
The FDA granted the accelerated approval based on DESTINY-Lung02, a multicenter, multi-cohort, randomized, blinded, dose-optimization trial. Eligible patients had to have unresectable or metastatic HER2-mutant non-squamous NSCLC with disease progression after prior systemic therapy. Patients were selected for treatment with Enhertu based on the presence of activating HER2 (ERBB2) mutations in a tumor specimen. Patients received Enhertu 5.4 mg/kg by intravenous infusion, every 3 weeks until unacceptable toxicity or disease progression.
Of the 52 patients in the primary efficacy population DESTINY-Lung02, the median age was 58 years (range 30 to 78), 69% were female; 79% were Asian, 12% were White, and 10% were of other races. The major efficacy outcome measures were confirmed objective response rate (ORR) as assessed by blinded independent central review using RECIST v1.1 and duration of response (DOR). The confirmed ORR was 58% (95% CI: 43, 71), and the median DOR was 8.7 months (95% CI: 7.1, not estimable [NE]).
On the safety side, it was found that the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea, decreased white blood cell count, decreased hemoglobin, decreased neutrophil count, decreased lymphocyte count, decreased platelet count, decreased albumin, increased aspartate aminotransferase, increased alanine aminotransferase, fatigue, constipation, decreased appetite, vomiting, increased alkaline phosphatase, and alopecia.
In addition to the newly approved indication, Enhertu poses the following indications:
Adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either: o in the metastatic setting, or o in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.
adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.
