GI Oncology Daily Digest

PERISCOPE II randomized 102 patients with resectable cT3/cT4a gastric adenocarcinoma and limited peritoneal metastases (Peritoneal Cancer Index <7) or positive cytology — none of whom had progressed after ≥3 cycles of systemic therapy — to continued systemic therapy alone versus gastrectomy plus cytoreductive surgery and HIPEC (oxaliplatin + docetaxel). After a median 67-month follow-up, median OS was 15.7 months in the surgery+HIPEC arm versus 16.6 months with systemic therapy alone (HR 1.10, 95% CI 0.69–1.74; p=0.70) — no benefit whatsoever. The aggressive arm came at a steep cost: grade ≥3 adverse events in 42% versus 20%, serious adverse events in 44% versus 6%, and three treatment-related deaths, all in the surgical arm. The trial closed early for futility. For a strategy that has quietly spread across referral centres, this is the definitive rebuttal: cytoreduction + HIPEC should not be offered outside a clinical trial for gastric cancer with limited peritoneal spread.

The EMA's human medicines committee (CHMP) has opened a phased review of daraxonrasib, Revolution Medicines' pan-RAS(ON) inhibitor, for metastatic pancreatic cancer that has progressed after prior therapy. A phased ('rolling') review lets the CHMP assess quality, nonclinical, and clinical data in stages as they become available, ahead of a full marketing-authorization application — compressing the path to a decision. The move rests on the positive RASolute 302 Phase 3 trial, which compared daraxonrasib with chemotherapy in previously-treated patients (published in NEJM; O'Reilly et al., doi 10.1056/NEJMoa2605555). Daraxonrasib already holds EMA orphan designation (April 2026) and high-priority status under the Cancer Medicines Pathfinder. For a disease where second-line options are dismal and life expectancy is roughly six months, this is the first concrete EU regulatory step for a RAS-targeted therapy in pancreatic cancer.

This Dana-Farber-led randomized, placebo-controlled window-of-opportunity trial gave 42 patients with stage I–III colon cancer either high-dose vitamin D3 (50,000 IU/day for 7 days, then 10,000 IU/day) or placebo before surgery, with paired pre/post spatial immune profiling in 24. Vitamin D significantly raised plasma 25-hydroxyvitamin D (p<0.001), increased intratumoral CD8+ memory T cells (p=0.03), reduced FoxP3+ regulatory T cells (p=0.02), and spatially reorganized the microenvironment to bring T cells and tumor cells into closer contact. Paradoxically, vitamin D receptor (VDR) expression fell overall (p=0.02) and spatial transcriptomics suggested predominantly repressive VDR activity after treatment. The takeaway: vitamin D is immunomodulatory in the human colon cancer microenvironment — a biological rationale for pairing it with immunotherapy — though this small trial is hypothesis-generating, not practice-changing.

This open-label randomized Phase II trial (NCT04734249) tested the oral VEGFR1-3/FGFR1/CSF-1R inhibitor surufatinib added to either doublet (FOLFOX/FOLFIRI) or triplet (FOLFOXIRI) chemotherapy as second-line treatment in 57 patients with metastatic colorectal cancer progressing after first-line doublet. The surufatinib-plus-doublet cohort showed encouraging activity — ORR 35.7%, median PFS 5.4 months, median OS 19.0 months — with manageable tolerability. The triplet cohort, despite a numerically higher ORR (39.3%), had more toxicity, more treatment discontinuations, and a substantially shorter median OS (10.9 months), and was explicitly not recommended for further study. The actionable read: if surufatinib advances in second-line mCRC, it belongs on a doublet backbone, not a triplet.