Multinational phase 2 trial of trastuzumab deruxtecan for HER2-mutant metastatic non-small-cell lung cancer

The multinational phase 2 DESTINY-Lung02 trial evaluated trastuzumab deruxtecan (T-DXd) at 5.4 mg/kg every three weeks and 6,4 mg/kg every three weeks among patients with HER2-mutant metastatic non-small cell lung cancer previously treated with platinum-based chemotherapy. The objective response rate was 49.0% with the lower dose versus 56.0% with the higher dose. Reponses were seen regardless of HER2 mutation type and amplification status. Grade ≥ 3 treatment-related adverse events were seen in 38.6% of patients with the lower dose versus 58.0% of patients with the higher dose. The median progression-free and overall survival were 9.9 months and 19.5 months with the lower dose, versus 15.4 months and not reached with the higher dose. The authors conclude that T-DXd demonstrated clinically meaningful responses at both doses. Safety profile was acceptable and generally manageable, favoring the 5.4 mg/kg dose.