Is T-DXd Active Against HER2-Mutant NSCLC?
Posted: Tuesday, October 26, 2021
For patients with HER2-mutant non–small cell lung cancer (NSCLC), treatment with the HER2 antibody-drug conjugate fam-trastuzumab deruxtecan-nxki demonstrated anticancer activity, according to the results of the multicenter international phase II DESTINY-Lung01 trial published in The New England Journal of Medicine. The safety profile of trastuzumab deruxtecan in this study was consistent with that of other studies, further supporting its efficacy in this type of lung cancer, explained Maurice Pérol, MD, of Léon Bérard Cancer Center, Lyon, France, and colleagues.
“These results support the clinical benefit of trastuzumab deruxtecan in patients with HER2-mutant NSCLC, a clinical context in which no targeted agents are currently approved,” commented the investigators.
A total of 91 patients with HER2-mutant NSCLC were enrolled in the study, and there was a median duration of follow-up of 13.1 months. All patients had metastatic or unresectable nonsquamous NSCLC and were either resistant to standard treatment or had relapsed during standard treatment. Patients received 6.4 mg/kg of body weight of trastuzumab deruxtecan intravenously every 3 weeks.
The study authors reported a centrally confirmed objective response in 55% of patients (95% confidence interval [CI] = 44%–65%). In addition, there was a 9.3-month median duration of response (95% CI = 5.7–14.7 months). The median overall survival for patients was 17.8 months (95% CI = 13.8–22.1 months), and the median progression-free survival was 8.2 months (95% CI = 6.0–11.9 months).
Moreover, 46% of patients experienced a grade 3 or higher drug-related adverse events, with the most reported event being neutropenia (in 19% of patients). Furthermore, 26% of patients experienced adjudicated drug-related interstitial lung disease, with two deaths considered to be attributable to treatment.
Disclosure: For full disclosures of the study authors, visit nejm.org.