Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02-A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC
Published report from the DESTINY-Lung02 trial registered as NCT04644237, in Journal of Thoracic Oncology (2025), chosen as the most cited paper whose own text cites the registry id.
Overview
Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes.
Methods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary end point was confirmed objective response rate by blinded independent central review.
Results: at August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1-Q3) was 15.8 (8.2-20.7) months and 16.5 (9.4-20.8) months, respectively. Confirmed objective response rate (95% confidence interval) was 50.0% (51/102; 39.9%-60.1%) and 56.0% (28/50; 41.3%-70.0%), respectively. Safety profile was acceptable and generally manageable. Accordingly, median treatment duration (Q1-Q3) was 7.7 (3.7-14.4) months and 8.3 (2.8-13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one grade 5 in each arm. Health-related quality of life was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on health-related quality of life observed at either dose.
Conclusions: T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose demonstrated a more favorable benefit-risk profile, including lower adjudicated drug-related interstitial lung disease incidence.
Gov identifier: NCT04644237.
Indexed on Europe PMC as PubMed record 40749900 (DOI 10.1016/j.jtho.2025.07.129). Its abstract cites the registry id NCT04644237, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT04644237 with the most citations, so it is the natural first reading for anyone following the DESTINY-Lung02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.