Trastuzumab deruxtecan tops ramucirumab + paclitaxel for 2L HER2-positive gastric cancer, lifting mOS to 14.7 mo

Trastuzumab deruxtecan (T-DXd), a HER2-directed antibody–drug conjugate, was pitted against standard ramucirumab + paclitaxel in the global phase 3 DESTINY-Gastric04 trial (NCT04704934). 494 patients with HER2-positive (IHC 2+ or 3+) metastatic gastric/GEJ adenocarcinoma who had progressed on trastuzumab were randomized 1:1 to T-DXd or ramucirumab plus weekly paclitaxel. Median overall survival was 14.7 months with T-DXd versus 11.4 months with the VEGF-inhibitor doublet (HR 0.70, P = 0.004); median PFS likewise favored T-DXd (HR 0.74). Confirmed ORR reached 44% vs 29%, and disease control 86% vs 81%. Grade ≥3 treatment-related AEs occurred in 50% and 54%, respectively.Adjudicated interstitial-lung-disease appeared in 13.9% of T-DXd patients (mostly grade 1-2, one grade 3). Compared with historical ramucirumab + paclitaxel outcomes from the RAINBOW trial (mOS 9.6 mo, ORR 28%), T-DXd delivers a ∼5-month survival edge and a 1.6-fold higher response without adding excess high-grade toxicity.