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.

Study Details

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.

Responses

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.

Adverse Events

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.