🍽️ GI Cancer — 2026-W44

What this page is. Every paper the week's monitor reviewed — including the ones that did not go into the digest. Material marked “Not selected” was reviewed and deliberately left out. It has not been fact-checked to digest standard and is not endorsed. For the curated read, see the digest itself.

Pragmatic phase 3 non-inferiority RCT in refractory metastatic colorectal cancer, published in The Lancet. Tests a simplified shorter schedule of trifluridine-tipiracil plus bevacizumab against the conventional schedule, informing whether toxicity can be reduced without losing survival benefit.

Phase 3 RCT in MSI-H/dMMR metastatic colorectal cancer, published in Annals of Oncology. Final analysis shows nivolumab plus ipilimumab improves overall survival over nivolumab and over first-line chemotherapy, supporting it as a preferred first-line immunotherapy option.

Randomized phase 1 dose-optimization study of a c-Met-directed antibody-drug conjugate plus bevacizumab versus trifluridine-tipiracil plus bevacizumab in heavily pretreated metastatic colorectal cancer, published in Annals of Oncology. Shows a manageable safety profile and encouraging responses regardless of c-Met selection, supporting further phase 3 development.

Randomized phase 2/3 trial in previously treated advanced biliary tract cancer, published in JCO. Adding tovecimig to paclitaxel improved response rate and progression-free survival without an overall survival difference, suggesting a potential new second-line option.

Open-label randomized phase 2 (MASTERPLAN) in previously untreated high-risk localised pancreatic adenocarcinoma, published in Lancet Oncology. Tests adding SBRT to perioperative chemotherapy (mFOLFIRINOX or gemcitabine/nab-paclitaxel) to reduce locoregional recurrence, informing the role of radiotherapy in this setting.

Randomized phase 3 trial of adjuvant cisplatin-gemcitabine versus capecitabine after resection of cholangiocarcinoma and gallbladder cancer, published in Annals of Oncology. The primary DFS comparison was not statistically significant by log-rank, though restricted mean survival analysis suggested some benefit, informing adjuvant choice in biliary cancer.

Cluster-randomised non-inferiority trial in locally advanced oesophageal cancer with complete clinical response after neoadjuvant chemoradiotherapy, published in Annals of Oncology. Long-term follow-up informs whether active surveillance can replace standard surgery, with attention to distant metastasis risk.

Phase 1/2 first-in-class bispecific T cell agonist (invikafusp alfa) monotherapy trial in mostly ICB-resistant solid tumors, published in Nature Medicine. Shows manageable safety and responses in immunologically cold tumors such as MSS colorectal cancer and PD-L1-negative NSCLC, supporting further development.

Narrative review of intrahepatic cholangiocarcinoma management published in JAMA Surgery, covering surgery, locoregional therapy, chemoimmunotherapy and targeted therapies. Provides an up-to-date overview of multimodal and systemic treatment options.

Narrative review in European Journal of Cancer on how evolving systemic therapy, including new direct RAS inhibitors, affects radiotherapy trials in pancreatic ductal adenocarcinoma. Informs future trial design and how RAS-targeted drugs may be integrated with local therapy.

Retrospective single-center real-world series of 177Lu-PRRT in advanced GEP-NETs, published in BMC Cancer. Describes effectiveness, short-term safety and retreatment outcomes, offering supportive though limited evidence for PRRT retreatment.

Randomized phase 2 trial of a mutant-KRAS-targeted amphiphile vaccine in stage I-III KRAS-mutated pancreatic adenocarcinoma after standard therapy, published in Nature Medicine. The primary DFS endpoint was not met, but subgroup and exploratory analyses (e.g., ctDNA-negative patients, T cell responses) suggest signals that may guide further development.

Randomized phase 2 trial in previously treated advanced esophageal squamous cell carcinoma, published in Nature Communications. Adding the anti-TIGIT antibody ociperlimab to tislelizumab did not significantly improve response, so it does not support this combination, though exploratory biomarkers hint at a benefit in inflamed tumors.

Single-arm phase 2 trial (NICHE-2) in previously untreated resectable dMMR colon cancer, published in The Lancet. Reports long-term disease-free and overall survival after short-course neoadjuvant immunotherapy, supporting this approach as a neoadjuvant strategy in dMMR disease.

International modified Delphi consensus on patient selection and management for perioperative FLOT in resectable gastric/GEJ cancer, published in JCO Oncology Practice. Offers practical guidance on eligibility, pre-treatment testing, and toxicity/nutrition management where existing guidelines are limited.

Multicenter retrospective cohort in dMMR/MSI-H colorectal cancer with clinical complete response to PD-1 inhibitors managed non-operatively, published in J Immunother Cancer. Compares observation versus maintenance immunotherapy for survival and toxicity, informing possible treatment de-escalation, though non-randomized and small.

Translational spatial and single-cell study in gastric cancer receiving neoadjuvant immunochemotherapy, published in J Immunother Cancer. Defines TLS archetypes that stratify immunotherapy response, but remains largely mechanistic and hypothesis-generating.

Single-arm multicenter phase 2 trial in previously treated advanced gastric/GEJ adenocarcinoma, published in BMC Cancer. Evaluates reduced-dose nab-paclitaxel with ramucirumab as a second-line option, informing dosing for patients who cannot tolerate full dose.

Single-arm multi-institutional phase 2 trial of hypofractionated proton beam therapy in unresectable HCC and intrahepatic cholangiocarcinoma, published in Clinical Cancer Research. Reports long-term outcomes with low toxicity and exploratory plasma signatures of progression, informing locoregional options but not systemic therapy.

Multiomic profiling study of microsatellite-stable colorectal cancer with tumoroid and xenograft validation, published in Cancer Cell. It nominates FAK, PDK1/2 and proteasome inhibition combined with MEK blockade in RAS-mutant disease as hypotheses, still preclinical.

Narrative review in NEJM on H. pylori history, pathogenesis, global burden, screening for gastric cancer prevention, and emerging management trends. Informs prevention strategy more than systemic treatment of established cancer.

Translational study in locally advanced EBV-associated gastric cancer, published in Nat Commun. Suggests neoadjuvant chemotherapy impairs tertiary lymphoid structure formation via EBV reactivation and neutrophil extracellular traps, with IM-TLS prognostic; mainly hypothesis-generating for future therapeutic targeting.

Preclinical translational study in gemcitabine-resistant pancreatic cancer models, published in Gastroenterology. Suggests mevalonate pathway inhibition with statins as a vulnerability after gemcitabine resistance, but remains hypothesis-generating pending clinical testing.