Mini-oral session – upper digestive tract cancers

For this video, Prof Hans Prenen, digestive oncologist at the Antwerp University Hospital, selected four abstracts presented during the mini-oral session on upper digestive tract cancers at ESMO 2025.

The first study consists of the PHERFLOT trial, a phase II study in the perioperative setting of HER2-positive, locally advanced gastric cancer. Current standards in the metastatic setting often combine HER2-directed therapy, such as trastuzumab, with chemotherapy and immune checkpoint blockade. The PHERFLOT trial extended this concept to the perioperative context by combining trastuzumab and pembrolizumab with the standard FLOT regimen. Treatment consisted of four cycles of FLOT with three cycles of trastuzumab and pembrolizumab before surgery, followed by the same combination after surgery, and maintenance trastuzumab with pembrolizumab for up to eleven additional cycles. Thirty-one patients were enrolled, making this a relatively small study, but the results were encouraging. The primary endpoint, pathologic complete response, was achieved in nearly half of the patients, signaling strong activity of this regimen. Although safety was broadly consistent with expectations, a notable incidence of grade 2 diarrhea was observed and warrants further monitoring in larger cohorts.¹

The phase II EDGE-Gastric study evaluated the combination of chemotherapy with domvanalimab, an anti-TIGIT antibody, and zimberelimab, an anti-PD-1 antibody, in the first-line treatment of patients with metastatic gastric cancer. The rationale for this trial stems from evidence that combining PD-1 blockade with TIGIT inhibition may enhance antitumor immunity. Long-term follow-up demonstrated a median overall survival of more than 20 months, an impressive signal in this disease context.² These findings have spurred ongoing phase III trials comparing similar PD-1/TIGIT combinations against nivolumab plus chemotherapy as the control arm. The outcome of these larger studies will be essential to determine the true clinical impact of this strategy.

The PERISCOPE-II study, conducted by the Dutch collaborative group, evaluated a rather controversial surgical approach. In patients with metastatic gastric cancer limited to peritoneal disease and with a low peritoneal cancer index (PCI <7), the trial compared continuation of chemotherapy alone against cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). After induction chemotherapy, around 100 patients were randomized. The trial showed no survival advantage with the addition of surgery and HIPEC. While some methodological limitations exist, the findings are clinically relevant, as this approach is still practiced in select centers despite the lack of robust evidence. The study strongly suggests that HIPEC does not confer benefit in this population, thereby discouraging its use outside of experimental settings.³

Finally, early-phase data were presented from a study of the claudin 18.2-targeted ADC RC118. The trial evaluated this ADC in combination with either PD-1 blockade (toripalimab) or a bispecific antibody targeting PD-1 and VEGF (RC148) in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer. The study demonstrated promising response rates with both strategies (33.3% and 57.1% for the combination with toripalimab and RC148, respectively).⁴ Although still in early clinical development, these results underscore the growing role of targeted ADCs and novel immunotherapy combinations in upper gastrointestinal cancers.