As reported in the Journal of Clinical Oncology by Goto et al, primary results of the phase II DESTINY-Lung02 trial have shown activity of fam-trastuzumab deruxtecan-nxki (T-DXd) in patients with HER2-mutant metastatic non–small cell lung cancer (NSCLC) previously treated with platinum-containing therapy.
An interim analysis of the trial supported the August 2022 approval of T-DXd at 5.4 mg/kg in this setting.
In the international trial, 152 patients were randomly assigned 2:1 between March 2021 and March 2022 to receive T-DXd at 5.4 mg/kg once every 3 weeks (n = 102) or at 6.4 mg/kg once every 3 weeks (n = 50). The primary endpoint was confirmed objective response rate on blinded independent central review.
Median duration of follow-up was 11.5 months (range = 1.1–20.6 months) in the 5.4-mg/kg group and 11.8 months (range = 0.6–21.0 months) in the 6.4-mg/kg group.
In the 5.4-mg/kg group, confirmed objective response was observed in 50 (49.0%, 95% confidence interval [CI] = 39.0%–59.1%) of 102 patients, with compete response seen in 1. An additional 45 patients (44.1%) had stable disease. Median duration of response was 16.8 months (95% CI = 6.4 months to not estimable).
In the 6.4-mg/kg group, confirmed objective response was observed in 28 (56.0%, 95% CI = 41.3%–70.0%) of 50 patients, with complete response seen in 2. An additional 18 patients (36.0%) had stable disease. Median duration of response was not estimable (95% CI = 8.3 months to not estimable).
Median progression-free survival on blinded independent central review was 9.9 months (95% CI = 7.4 months to not estimable) in the 5.4-mg/kg group and 15.4 months (95% CI = 8.3 months to not estimable) in the 6.4-mg/kg group; rates at 12 months were 45% and 53%, respectively.
Grade ≥ 3 treatment-related adverse events occurred in 38.6% of patients in the 5.4-mg/kg group and in 58.0% of those in the 6.4-mg/kg group. The most common events were neutropenia (18.8%), anemia (10.9%), and fatigue (7.9%) in the 5.4-mg/kg group, and neutropenia (36.0%), anemia (16.0%), and leukopenia (16.0%) in the 6.4-mg/kg group. Adjudicated drug-related interstitial lung disease occurred in 12.9% and 28.0% of patients (grade ≥ 3 in 2.0% of each group).
The investigators concluded, “T-DXd demonstrated clinically meaningful responses at both doses. [The] safety profile was acceptable and generally manageable, favoring T-DXd [at] 5.4 mg/kg.”
Koichi Goto, MD, PhD, of National Cancer Center Hospital East, Chiba, Japan, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Daiichi Sankyo in collaboration with AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.