Results from the phase II DESTINY-Lung 01 trial of fam-trastuzumab deruxtecan-nxki demonstrated robust and long-lasting antitumor activity among patients with previously treated human epidermal growth factor receptor 2 (HER-2) mutated nonÐsmall cell lung cancer (NSCLC). The results were published simultaneously in the New England Journal of Medicine.
In the study, Li et al explored the efficacy and safety of fam-trastuzumab deruxtecan-nxki, which is a HER2 antibody drug conjugate for the treatment of patients with HER2-mutant NSCLC. Primary results from the HER2m cohort (cohort 2) of DESTINY-Lung01 in previously treated HER2m NSCLC demonstrated a confirmed objective response rate of 54.9% in patients treated with trastuzumab deruxtecan (6.4 mg/kg) as assessed by independent central review.
One (1.1%) complete response and 49 (53.8%) partial responses were observed. A confirmed disease-control rate of 92.3% was detected, with a reduction in tumor size observed in most patients. The results from the phase II DESTINY-Lung 01 trial were presented at the 2021 virtual European Society for Medical Oncology Congress.
After a median follow-up of 13.1 months, the median duration of response for fam-trastuzumab deruxtecan-nxki was 9.3 months. The median progression-free survival was 8.2 months, and the median overall survival was 17.8 months. The safety profile was generally consistent with those from previous studies with no new safety signals.
The most common grade 3 or higher drug-related, treatment-emergent adverse events were neutropenia (18.7%) and anemia (9.9%). Rates of treatment-related interstitial lung disease (ILD) and pneumonitis were consistent with those in previous trials in lung cancer. There were 24 cases of ILD or pneumonitis, as determined by an independent adjudication committee, with the majority (75%) low grade (grade 1 or 2) and four grade 3 and two grade 5 (ILD or pneumonitis-related death). Responses were observed across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification.
The authors concluded that the use of fam-trastuzumab deruxtecan-nxki demonstrated durable anticancer activity in patients with previously treated HER2-mutant NSCLC. To further optimize the dosing regimen of fam-trastuzumab deruxtecan-nxki in this patient population, the 5.4-kg/mg dosage is being evaluated in the phase ll DESTINY-Lung02 trial.
Lead author Bob Li, MD, PhD, MPH, Memorial Sloan Kettering Cancer Center, stated, "Despite more than 20 years of research into HER2-mutations in non-small cell lung cancer, there are currently no approved HER2-targeted therapies for non-small cell lung cancer. Patients with HER2-mutant non-small cell lung cancer are associated with younger age, female sex, never smoking history and a poor prognosis with increased incidence of brain metastases, representing unmet clinical need. The impressive results from DESTINY-Lung01 showed most patients experienced a reduction in tumor size with Enhertu treatment, suggesting this medicine has the potential to become the new standard of care for these patients."
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