Trastuzumab deruxtecan demonstrated an acceptable safety profile and was associated with a clinically significant objective response rate in patients with HER2-mutant metastatic non-small-cell lung cancer in a phase II study.
Human epidermal growth factor receptor (HER2) mutations are present in a small number of non-squamous non-small-cell lung cancer (NSCLC) patients. Trastuzumab deruxtecan (T-DXd) is approved for the treatment of HER2-mutant metastatic NSCLC and is known to be effective in multiple types of cancer.
A multicenter phase II study investigated the objective response rate in patients with HER2 mutant metastatic NSCLC with doses of 5.4 mg/kg and 6.4 mg/kg of T-DXd. The study findings are published in the Journal of Clinical Oncology.
Study Participants
The study included 152 patients, with 102 and 50 patients randomized to T-DXd 5.4 mg/kg once per three weeks and T-DXd 6.4 mg/kg once per three weeks, respectively. In the T-DXd 5.4 mg/kg once per three weeks cohort, the median age of participants was 59.4 (31–84) years, and 36.3% were male. In the T-DXd 6.4 mg/kg once per three weeks cohort, the median age of participants was 61.3 (28–86) years, and 32.0% were male. The prevalence of HER2 mutations in the kinase domain among the T-DXd 5.4 mg/kg and 6.4 mg/kg cohorts was 97.1% and 100%, respectively.
Efficacy of Trastuzumab Deruxtecan
The confirmed objective response rate in the T-DXd 5.4 mg/kg and 6.4 mg/kg cohorts was 49.0% and 56.0%, respectively. Patients in both cohorts demonstrated a decrease in tumor size compared to baseline. For T-DXd 5.4 mg/kg, the median duration of response was 16.8 months and the median duration for initial response was 1.8 (1.2-7.0) months. For T-DXd 6.4 mg/kg, the median duration of response was NE, and the median duration for the initial response was 1.6 (1.2-11.2) months.
Trastuzumab Deruxtecan and Patient Survival Outcomes
The median progression-free survival was 9.9 (7.4–not estimable (NE)) months and 15.4 (8.3–NE) months in the T-DXd 5.4 mg/kg and 6.4 mg/kg cohorts, respectively. The progression-free survival at 12 months was 45% and 53% with T-DXd 5.4 mg/kg and 6.4 mg/kg doses, respectively.
Safety Profile of Trastuzumab Deruxtecan
The most frequent treatment-emergent adverse events (TEAEs) in both cohorts were nausea, neutropenia, fatigue, and reduced appetite. Anemia and neutropenia were the most frequent grade ≥ 3 adverse events. Grade ≥ 3 TEAEs occurred in approximately 38.6% and 58.0% of patients administered T-DXd 5.4 mg/kg and 6.4 mg/kg doses, respectively. Interstitial lung disease was reported in approximately 12.9% and 28.0% of patients given T-DXd 5.4 mg/kg and 6.4 mg/kg doses, respectively.
Source:
Goto, K., Goto, Y., Kubo, T., Ninomiya, K., Kim, S., Planchard, D., Ahn, M., Smit, E. F., De Langen, A. J., Pérol, M., Pons‐Tostivint, E., Novello, S., Hayashi, H., Shimizu, J., Kim, D., Kuo, C. S., Yang, J. C., Pereira, K., Cheng, F., . . . Jänne, P. A. (2023). Trastuzumab deruxtecan in patients with HER2-Mutant metastatic Non–Small-Cell lung cancer: primary results from the randomized, Phase II DESTINY-LuNG02 trial. Journal of Clinical Oncology, 41(31), 4852–4863. https://doi.org/10.1200/jco.23.01361
