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

Study Details

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.

Responses

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).

Adverse Events

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.