N Engl J Med 2021 Sep 18
Trastuzumab Deruxtecan in -Mutant Non-Small-Cell Lung Cancer.
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.).
Related Questions
How does trastuzumab deruxtecan compare to other HER2 targeted strategies?
New comment by Medical Oncologist at St. Luke's Episcopal Hospital ( November 16, 2021)
Pulmonary fibrosis is a known toxicity of this drug. So it is best to avoid this drug for patients who have any preexisting pulmonary fibrosis.
How are you thinking about sequencing therapies for these patients (IO vs chemo vs T-Dxd)? Are the data from DESTINY-Lung01 strong enough to warrant e...
New answer by Medical Oncologist at Lung Cancer Research Foundation (LCRF) (November 9, 2021)
My usual approach is chemo plus IO with HER2 therapy i.e., T-Dxd as a second line treatment. The DESTINY data are strong but because this is a Phase 2 study, I would prefer to...
How and when do you plan to perform HER2 testing in patients with NSCLC?
New answer by Medical Oncologist at Lung Cancer Research Foundation (LCRF) (November 26, 2021)
The results with HER2 mutations are more reliable than the protein expression. I perform HER2 testing with my NGS at diagnosis because we did have some trials.
New comment by Medical Oncologist at Northwest Georgia Oncology Centers ( November 13, 2022)
I am assuming that this patient was on maintenance durva? Would you consider using chemo + IO before using Enhertu?
And for some reason (patient preference?) durva was ...