Proffered paper session (2)

In this video, Prof Dr Jeroen Dekervel discusses three studies presented during a Proffered Paper session at ESMO GI 2026, covering new data in metastatic colorectal cancer and gastric/gastro-oesophageal cancer.

The phase III KRYSTAL-10 trial evaluated adagrasib plus cetuximab versus chemotherapy, with or without anti-VEGF/VEGFR therapy, as second-line treatment for KRAS G12C-mutated metastatic colorectal cancer.¹ At final analysis, neither dual primary endpoint was met: median overall survival (OS) was 21.6 versus 21.7 months (HR=0.83; p=0.094) and median progression-free survival (PFS) was 7.5 versus 8.1 months (HR=0.89; p=0.324) for adagrasib plus cetuximab versus chemotherapy, respectively. Objective response rate (ORR) was higher with the combination (47% versus 16%), including more complete responses (7% versus <1%), but this did not translate into a survival benefit. This may reflect rapid emergence of resistance in this pretreated setting. Trials evaluating KRAS G12C inhibitors earlier in the treatment course are ongoing.

A second phase III trial, STAR-221, assessed the addition of TIGIT blockade to first-line treatment of HER2-negative advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma.² The trial randomised 1,040 patients to domvanalimab (anti-TIGIT) plus zimberelimab (anti-PD-1) and chemotherapy versus nivolumab plus chemotherapy. Despite encouraging phase II data with the combination, the trial did not meet its primary OS endpoint in the intention-to-treat population (14.0 versus 13.4 months; HR=1.01; p=0.526), nor in the PD-L1-high (TAP ≥5%) or PD-L1-positive (TAP ≥1%) populations. PFS and ORR (55% versus 56%) were likewise comparable between arms. These data indicate that TIGIT inhibition is unlikely to change first-line treatment practice in HER2-negative advanced gastro-oesophageal adenocarcinoma.

The third presentation reported patient-reported health-related quality-of-life (HRQoL) outcomes from HERIZON-GEA-01, a phase III trial in first-line HER2-positive gastro-oesophageal adenocarcinoma.³ The trial previously demonstrated a significant PFS improvement with zanidatamab plus chemotherapy, with or without tislelizumab, versus trastuzumab plus chemotherapy (12.4 months in both zanidatamab-containing arms versus 8.1 months), together with a significant OS benefit for the triplet regimen (26.4 versus 19.2 months; HR=0.72; p=0.0043). In the HRQoL analysis, EORTC QLQ-C30 global health status/quality-of-life and functional scores showed no substantive change from baseline in any arm, with no meaningful differences between treatment groups over time. Diarrhoea, the most frequent treatment-related adverse event with zanidatamab-containing regimens, was reflected in patient-reported symptom scores. These worsened modestly during the early cycles, coinciding with concurrent chemotherapy, before improving and stabilising once chemotherapy could be discontinued after cycle 6.