Disitamab vedotin plus programmed death-1 inhibitor for pre-treated HER2 overexpressed advanced gastric cancer: a multicentre retrospective real-world study

The efficacy of pre-treated advanced gastric or gastroesophageal junction cancer (G/GEJC) with HER2 overexpressed (IHC 2+/3+) remains unsatisfactory. This retrospective real-world study aimed to analyse the safety and efficacy of disitamab vedotin (RC48) plus programmed death-1 (PD-1) inhibitor in pre-treated patients with advanced G/GEJC. We retrospectively reviewed consecutive patients with HER2 2+/3+ advanced G/GEJC who received RC48 plus PD-1 inhibitor or RC48 monotherapy from four Chinese hospitals (July 2021 to September 2023). ORR and DCR were estimated by logistic regression. Survival was analysed via Kaplan-Meier method and log-rank tests. Subgroup and <i>post hoc</i> power analyses were performed. Fifty-seven patients were enrolled: 36 received RC48 plus PD-1 inhibitor (combination group) and 21 received RC48 alone (monotherapy group). The combination group demonstrated a significantly higher ORR than the monotherapy group (41.7% vs. 9.5%, <i>p</i> = 0.011). Although the DCR was not significantly different (75.0% vs. 57.1%, <i>p</i> = 0.162), the combination group showed a significantly prolonged mOS (13.2 months vs. 7.1 months, <i>p</i> = 0.040) and a trend towards longer mPFS (5.8 months vs. 2.9 months, <i>p</i> = 0.142). In the combination group, patients with initial HER2 3+, second-line treatment, or liver metastasis had more favourable outcomes. The incidence of grade 3–4 TrAEs was comparable between the two groups (41.7% vs. 38.1%). RC48 plus PD-1 inhibitor for pre-treated advanced G/GEJC patients with HER2 2+/3+ demonstrated superior efficacy than RC48 monotherapy and favourable safety. This combination represents a potential therapeutic strategy, but further large-scale prospective studies are still needed.