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Trastuzumab Deruxtecan Superior to Chemo for HER2+ Gastric Cancer, GEJ Adenocarcinoma
A final overall survival (OS) analysis from the randomized, open-label, phase 2 DESTINY-Gastric01 trial of trastuzumab deruxtecan found it has a statistically significant benefit over standard chemotherapy in patients with HER2-positive advanced gastric cancer or GEJ adenocarcinoma.
“Trastuzumab deruxtecan is an antibody-drug conjugate comprising of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a topoisomerase I inhibitor,” explained Kensei Yamaguchi, MD, The Cancer Institute Hospital of JFCR, Japan, and co-researchers.
The multicenter trial enrolled a total of 187 patients with locally advanced or metastatic, centrally confirmed HER2-positive gastric cancer or GEJ adenocarcinoma that progressed after 2 or more prior lines of therapy including trastuzumab, and were randomly assigned to 2:1 (trastuzumab deruxtecan 6.4 mg/kg every 3 weeks or physician’s choice (of irinotecan or paclitaxel).
The primary endpoint was overall response rate (ORR) by independent key review. Secondary endpoints included OS, duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), confirmed ORR, and safety.
Dr Yamaguchi and co-researchers continued, “125 patients received trastuzumab deruxtecan and 62 received their physician’s choice of regimen. 79.7% of patients were Japanese and 20.3% were Korean. At data cutoff, 8% of trastuzumab deruxtecan and 0% of PC patients remained on treatment (median survival follow-up, 18.5 months).”
The researchers reported improved OS with trastuzumab deruxtecan versus physician’s choice (median OS, 12.5 versus 8.9 months; hazard ratio [HR], 0.60; 95% CI, 0.42-0.86). The 12-month OS was 52.2% versus 29.7%. The ORR was 51.3% with trastuzumab deruxtecan versus 14.3% with physician’s choice (P < 0.0001). Confirmed ORR was 42% versus 12.5%, respectively. DCR was 85.7% versus 62.5%, and median PFS was 5.6 versus 3.5 months.
Notably, the median DOR was 12.5 months in patients who received trastuzumab deruxtecan and was 3 times longer than standard chemotherapy, which was 3.9 months.
Reported grade 3 or higher adverse events (AEs) occurred in 85.6% of trastuzumab deruxtecan patients versus 56.5% with physician’s choice. The most common AEs were neutrophil count decreased (51.2%, 24.2%), anemia (38.4%, 22.6%), and white blood cell count decreased (20.8%, 11.3%). The median time to first onset of AEs was 102.5 days.
“With additional follow-up after the primary analysis, trastuzumab deruxtecan continued to demonstrate OS benefit and clinically relevant improvement in ORR compared with standard chemotherapy, and a manageable safety profile, in HER2-positive advanced gastric cancer or GEJ adenocarcinoma,” concluded Dr Yamaguchi, et al.—Alexa Stoia
Yamaguchi K, Bang Y-J, Iwasa S, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Final overall survival (OS) results from a randomized, multicenter, open-label, phase 2 study (DESTINY_Gastric01). Presented at ASCO GI 2022; January 20-22, 2022. Abstract 242.
