Dr Jänne on Trastuzumab Deruxtecan in HER2-Mutant NSCLC

Pasi A. Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology, director, Belfer Center for Applied Cancer Science, director, Chen-Huang Center for EGFR Mutant Lung Cancers, senior physician, Dana-Farber Cancer Institute; professor, medicine, Harvard Medical School, discusses key findings from the primary analysis of the phase 2 DESTINY-Lung02 trial (NCT04644237) in patients with HER2-mutant non–small cell lung cancer (NSCLC), which he presented during the 2023 IASLC World Conference on Lung Cancer.

DESTINY-Lung02 is a randomized, multicenter, international trial investigating the efficacy and safety of fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with metastatic NSCLC harboring HER2 mutations who have received at least 1 prior therapy. Patients were randomly assigned 2:1 to receive trastuzumab deruxtecan at either 5.4 mg/kg every 3 weeks or 6.5 mg/kg every 3 weeks.

The confirmed overall response rates (ORRs) were 49.0% (95% CI, 39.0%-59.1%) in the 5.4 mg/kg arm and 56.0% (95% CI, 41.3%-70.0%) in the 6.4 mg/kg arm. In the 5.4 mg/kg arm, the complete response (CR) and partial response (PR) rates were 1.0% and 48.0%, respectively. In the 6.4 mg/kg arm, the respective CR and PR rates were 4.0% and 52.0%.

The ORRs in both arms of DESTINY-Lung02 are similar to those seen in the phase 2 DESTINY-Lung01 trial (NCT03505710), Jänne says. DESTINY-Lung-01 investigated trastuzumab deruxtecan at a dose of 6.4 mg/kg in patients with HER2-mutant NSCLC. In this trial, trastuzumab deruxtecan elicited an ORR of 55% (95% CI, 44%-65%).

In DESTINY-Lung02, the safety profile of trastuzumab deruxtecan was favorable with the 5.4 mg/kg dose. Patients in the 5.4 mg/kg arm experienced a lower incidence of any-grade, drug-related interstitial lung disease, at 12.9% vs 28.0% in the 6.4 mg/kg arm.

These efficacy and safety findings continue to support the use of trastuzumab deruxtecan in patients with HER2-mutant NSCLC, Jänne explains. The 5.4 mg/kg dose of the agent administered every 3 weeks delivers a favorable balance of efficacy and tolerability, and is the approved dose in the United States, Jänne emphasizes. In 2022, the FDA granted accelerated approval to trastuzumab deruxtecan for patients with HER2-mutant NSCLC based on the findings from DESTINY-Lung02, marking it as the first drug approved for patients with HER2-mutant NSCLC.