AI Article Synopsis
- - A phase 2 study tested trastuzumab deruxtecan, a HER2-targeted therapy, in patients with metastatic non-small-cell lung cancer (NSCLC) who were unresponsive to standard treatments, focusing on its efficacy and safety.
- - Out of 91 patients, 55% showed an objective response to the treatment, with a median response duration of 9.3 months and overall survival of 17.8 months; however, severe adverse effects occurred in 46% of participants.
- - The study found effective responses across various mutation subtypes and in some patients without detectable HER2 alterations, but also highlighted serious safety concerns, including fatal cases of interstitial lung disease.
Article Abstract
Background: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have not been approved for patients with non-small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody-drug conjugate, in patients with -mutant NSCLC have not been investigated extensively.
Methods: We conducted a multicenter, international, phase 2 study in which trastuzumab deruxtecan (6.4 mg per kilogram of body weight) was administered to patients who had metastatic -mutant NSCLC that was refractory to standard treatment. The primary outcome was objective response as assessed by independent central review. Secondary outcomes included the duration of response, progression-free survival, overall survival, and safety. Biomarkers of HER2 alterations were assessed.
Results: A total of 91 patients were enrolled. The median duration of follow-up was 13.1 months (range, 0.7 to 29.1). Centrally confirmed objective response occurred in 55% of the patients (95% confidence interval [CI], 44 to 65). The median duration of response was 9.3 months (95% CI, 5.7 to 14.7). Median progression-free survival was 8.2 months (95% CI, 6.0 to 11.9), and median overall survival was 17.8 months (95% CI, 13.8 to 22.1). The safety profile was generally consistent with those from previous studies; grade 3 or higher drug-related adverse events occurred in 46% of patients, the most common event being neutropenia (in 19%). Adjudicated drug-related interstitial lung disease occurred in 26% of patients and resulted in death in 2 patients. Responses were observed across different mutation subtypes, as well as in patients with no detectable HER2 expression or amplification.
Conclusions: Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated -mutant NSCLC. The safety profile included interstitial lung disease that was fatal in two cases. Observed toxic effects were generally consistent with those in previously reported studies. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710.).
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066448 | PMC |
| http://dx.doi.org/10.1056/NEJMoa2112431 | DOI Listing |
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