Gastrointestinal Oncology Research Updates

In a phase 3 randomized self-controlled trial of mostly regorafenib-treated patients with unresectable colorectal cancer, GIST, or hepatocellular carcinoma, prophylactic hydrocolloid dressing plus standard moisturizing versus moisturizing alone reduced the incidence of grade ≥2 foot hand–foot skin reaction (20% vs 50%, p<0.0001) and delayed time to grade ≥2 HFSR (HR 0.32, p=0.0017), with lower patient-reported HFSR severity. The study supports hydrocolloid dressing as an effective prophylactic measure against HFSR in this population.

The author reviews evidence that hepatocellular carcinoma patients who respond to anti-PD-1 therapy show enrichment and clonal expansion of IgG1-producing plasma cells and upregulation of IGHG1. Given known links between IgG1 GM (γ marker) allotypes, IgG subclass levels, autoantibody responses, and antibody-dependent cellular cytotoxicity, the paper hypothesizes that GM allotypes on IgG1 could serve as genetic markers of response to anti-PD-1 and other checkpoint blockade therapies characterized by IgG1-skewed plasma cell expansion.

The commentary reviews dual PD-L1/TGF-β targeting in light of the approval of retlirafusp alfa (SHR-1701) in China for first-line PD-L1–positive advanced gastric or gastroesophageal junction adenocarcinoma with chemotherapy, noting that TGF-β–driven immune suppression is spatially organized within stromal niches, varies across indications, and may not be the dominant barrier even when PD-L1 is expressed. The authors argue SHR-1701's approval provides proof of principle and supports mechanism-aligned development using biomarker-based selection, rational combinations/sequencing and pharmacodynamic endpoints to test target engagement and benefit.