Trastuzumab Deruxtecan Versus Ramucirumab-Paclitaxel as Second-Line Therapy for Patients With HER2-Positive Gastric or GEJ Adenocarcinoma

Background: The single-arm phase II DESTINY-Gastric02 (DG-02) study investigated trastuzumab deruxtecan (T-DXd) as second-line therapy in Western patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma that progressed during or after trastuzumab-based first-line therapy. The aim of the current study was to compare patients in the DG-02 study with a real-world reference group of patients who received ramucirumab and paclitaxel (Ram + Pac) as second-line therapy. Methods: A total of 71 of 79 patients from DG-02 who had received trastuzumab in the metastatic setting were included. A comparable cohort of patients with HER2-positive esophageal, gastric, or GEJ adenocarcinoma who received trastuzumab in the first-line setting and Ram + Pac in the second-line setting was identified from the Netherlands Cancer Registry (NCR; n=120). Propensity score trimming and propensity score were used to select a reference group for DG-02 from patients in the NCR, based on sex, age, ECOG performance status, primary tumor location, body mass index, renal function, number of metastatic sites, presence of liver metastases, and duration of first-line therapy. Results: Propensity score trimming led to the exclusion of 12 patients from the DG-02 group and 33 patients from the NCR group. Thereafter, propensity score matching resulted in a balanced group of patients from the NCR (n=78) and the DG-02 trial (n=58). Median overall survival was significantly longer among patients treated with T-DXd (11.6 months; 95% CI, 9.0–20.5) compared with those treated with the Ram + Pac reference regimen (6.2 months; 95% CI, 4.5–10.0; P <.0001). Conclusions: Compared with patients with metastatic, trastuzumab-pretreated HER2-positive gastric or GEJ adenocarcinoma who received Ram + Pac, those who received T-DXd as second-line therapy had improved overall survival.