Anbenitamab in previously treated HER2-positive gastric cancer (KC-WISE): pre-specified interim analysis of a randomized, phase III clinical trial
Mené en Chine sur 188 patients atteints d'un cancer gastrique ou d'un adénocarcinome de la jonction oesogastrique HER2+ ayant progressé après un traitement par trastuzumab, cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité de l'ajout d'anbénitamab à une chimiothérapie
Background: Gastric cancer after progression on trastuzumab treatment remains an unmet therapeutic challenge and is associated with suboptimal progression-free survival (PFS) and overall survival (OS).
Patients and methods: This multicentre, randomised, double-blind, phase 3 trial was conducted at 51 hospital sites in China. Patients with HER2-positive gastric cancer or gastro-oesophageal junction (GC/GEJ) adenocarcinoma whose previous therapy containing trastuzumab had failed were randomised (1:1) to receive anbenitamab 30 mg/kg or placebo every 3 weeks, in combination with chemotherapy (paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on day 1 of a 21-day cycle, or irinotecan 125 mg/m2 on day 1 and 8 of a 21-day cycle), stratified by combined chemotherapy (taxane [paclitaxel or docetaxel] or irinotecan), HER2 expression (IHC 3+ or IHC 2+/FISH+), and previous lines of therapy (1 or ≥2). Primary endpoints were independent review committee-assessed PFS and OS in the intention-to-treat population. This interim analysis was planned when approximate 120 PFS events were observed.
Results: A total of 188 patients were enrolled and assigned to receive anbenitamab plus chemotherapy (anbenitamab group, n=95) or chemotherapy alone (control group, n=93). At the prespecified interim analysis, anbenitamab plus chemotherapy significantly improved PFS (median [95% confidence interval (CI)], 7.1 [5.5–10.3] vs 2.7 [1.5–3.0] months; hazard ratio [HR], 0.25; 95% CI, 0.17–0.39; p<0.0001) and OS (median [95% CI], 19.6 [15.0–not evaluable] vs 11.5 [6.5–14.4] months; HR, 0.29; 95% CI, 0.17–0.50; p<0.0001) compared with chemotherapy alone. Grade 3 or higher treatment-related adverse events occurred in 56 (60%) of 94 patients who received anbenitamab plus chemotherapy and 42 (45%) of 93 patients who received chemotherapy alone, with neutropenia (30% vs 22%) and leukopenia (21% vs 25%) being most common. Treatment-related deaths were reported in 0 and 5 patients in the anbenitamab and control groups, respectively.
Conclusions: Compared with chemotherapy alone, anbenitamab plus chemotherapy demonstrated clinically meaningful superior PFS and OS in patients with HER2-positive GC/GEJ adenocarcinoma whose previous therapy containing trastuzumab had failed. These findings warrant confirmation in the final analysis.
Annals of Oncology , résumé, 2026