In the phase II DESTINY-Gastric02 trial reported in The Lancet Oncology, Eric Van Cutsem, MD, PhD, and colleagues found that fam-trastuzumab deruxtecan-nxki (T-DXd) was active in patients with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen.
Eric Van Cutsem, MD, PhD
In the study, 79 patients with unresectable or metastatic disease with disease progression on or after first-line therapy with a trastuzumab-containing regimen were enrolled from sites in the United States and Europe between November 2019 and December 2020. Patients received T-DXd at 6.4 mg/kg every 3 weeks until disease progression, withdrawal, or physician decision. The primary endpoint was confirmed objective response rate on independent central review.
At primary analysis, with a median follow-up of 5.9 months (interquartile range [IQR] = 4.6–8.6 months), confirmed objective response was observed in 30 of 79 patients (38%, 95% confidence interval [CI] = 27.3%–49.6%), including a complete response in 3 (4%). Stable disease was observed in an additional 34 patients (43%); the disease control rate was 81%. Median response duration was 8.1 months (95% CI = 4.1 months to not estimable). Median progression-free survival was 5.5 months (95% CI = 4.2–7.2 months), and median overall survival was 12.1 months (95% CI = 8.6 months to not estimable).
In an updated analysis, with a median follow-up of 10.2 months (IQR = 5.6–12.9 months), confirmed objective response was observed in 33 of 79 patients (42%, 95% CI = 30.8%–53.4%), including a complete response in 4 (5%). Stable disease was observed in an additional 31 patients (39%); the disease control rate was 81%. Median response duration was 8.1 months (95% CI = 5.9 months to not estimable). Median progression-free survival was 5.6 months (95% CI = 4.2–8.3 months), and median overall survival was 12.1 months (95% CI = 9.4–15.4 months).
At the time of the updated analysis, grade ≥ 3 adverse events had occurred in 56% of patients, most commonly anemia (14%), nausea (8%), and decreased neutrophils (8%). Serious adverse events occurred in 42% of patients and were considered treatment-related in 13%. Adverse events led to treatment discontinuation in 19% of patients. Death considered related to treatment occurred in two patients (3%), from interstitial lung disease and pneumonitis in both.
The investigators concluded: “These clinically meaningful results support the use of [T-DXd] as second-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer.”
Dr. Van Cutsem, of University Hospitals Gasthuisberg, University of Leuven, Belgium, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Daiichi Sankyo and AstraZeneca. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.