Oral abstract session: Cancers of the oesophagus and stomach

The Chinese, randomised, phase II NEOSUMMIT-01 trial evaluated perioperative chemotherapy with or without the PD-1 antibody toripalimab in patients with locally advanced, resectable gastric or gastro-oesophageal junction (GEJ) adenocarcinoma. The addition of toripalimab increased the pathological complete response rate from 7% with chemotherapy alone to 22% with the chemo-immunotherapy combination. While longer follow-up is needed to determine the impact on survival outcomes, these results support the activity of perioperative chemo-immunotherapy in this setting.

The Dutch, phase II CRITICS-II study compared three neoadjuvant strategies in locally advanced gastric and GEJ adenocarcinoma: neoadjuvant chemotherapy alone, neoadjuvant chemoradiotherapy (CRT) alone, and neoadjuvant chemotherapy followed by CRT, all followed by surgery. The sequential approach combining chemotherapy followed by CRT appeared more effective than either modality alone. Interpretation for daily practice remains challenging, as the study design does not incorporate postoperative chemotherapy, and therefore differs from widely used perioperative strategies.

The non-randomised phase II ILUSTRO trial investigated first-line treatment in metastatic gastric or GEJ adenocarcinoma by combining chemotherapy with the CLDN18.2-targeting antibody zolbetuximab and nivolumab. Patients with tumours that were both CLDN18.2-positive and PD-L1-positive appeared to achieve encouraging outcomes. While these findings are not practice-changing at this stage, they provide supportive evidence that dual targeting of CLDN18.2 and PD-1 may be an effective approach in a biomarker-enriched population. The ongoing phase III Lucerna trial is further evaluating the combination of zolbetuximab, immunotherapy and chemotherapy in patients with gastric and GEJ adenocarcinoma.

Finally, HERIZON-GEA-01 was a phase III first-line study in metastatic HER2-positive gastric, GEJ and oesophageal adenocarcinoma. Patients were randomised between chemotherapy plus trastuzumab or experimental arms including zanidatamab, a bispecific HER2 antibody, with or without the addition of tislelizumab. The combination of chemotherapy, zanidatamab and the checkpoint inhibitor tislelizumab demonstrated a clinically meaningful and statistically significant survival advantage compared with chemotherapy plus trastuzumab with a median overall survival extending beyond two years. The zanidatamab plus chemotherapy arm also appeared numerically favourable but was not yet significant at the time of this interim analysis, requiring longer follow-up. Overall, these results strongly suggest a shift toward a new standard of care in first-line HER2-positive metastatic disease, pending regulatory approval and accessibility of zanidatamab-containing regimens.