GI Oncology Digest Archive

Mosperafenib — first "paradox-breaker" BRAF inhibitor in 80 BRAFᵛ⁶⁰⁰ solid tumor patients with 79% CRC representation, ORR 24% and mPFS 6.4 mo in CRC, brain-penetrant, no PPE/KA (JCO Phase Ia/b); Phase II progression-directed RT continued alongside first-line systemic therapy in oligoprogressive HCC delivers mPFS 7.0 mo / ORR 64.7% / 1-yr OS 86.4% across 10 Chinese cancer centers (Clin Cancer Res); Bardelli lab shows MSS-CRC evades immune surveillance via a secretome-driven, glycosylation-dependent program independent of neoantigen load (Cancer Discovery); robotic vs laparoscopic low anterior resection meta-analysis of 82,149 patients confirms lower conversion, 30-day mortality and better complete TME (J Robot Surg); and a 12-metabolite plasma signature derived from 1,706 samples achieves AUC 0.951 for gastric cancer detection (Nat Commun).

EMERALD-3 Phase III — durvalumab + tremelimumab + lenvatinib + TACE significantly improves PFS in embolization-eligible unresectable HCC (AstraZeneca), daraxonrasib full Phase 1/2 publication in 2L KRAS-mutant PDAC (NEJM, 35% ORR / 13.1-mo OS), HER2 discordance between primary and metastatic gastric cancer pooled meta-analysis (Clin Transl Oncol — 13% primary vs 18% mets, 38% lung / 31% liver), 20-year SEER-Medicare analysis showing perioperative chemo cuts mortality in resected CRC liver metastases by 46% (Surgery), and a mechanism for why CLDN18.2 therapy stalls in KRAS-mutant PDAC with a precision rescue strategy (Gut).

Cancer Screening Special Edition pulling together five recent papers that, taken together, reshape how we think about GI cancer early detection: NORCCAP 23-year follow-up (Annals of Internal Medicine) shows single-sigmoidoscopy still cutting CRC incidence and mortality in men two decades later, NORDICC 13-year follow-up (Lancet) shows single colonoscopy cuts CRC incidence but mortality benefit remains elusive, REDMOD AI radiomics on standard-of-care CT (Gut, Mayo Clinic) detects occult pancreatic cancer ~475 days pre-diagnosis with sensitivity nearly twofold higher than expert radiologists, abbreviated non-contrast MRI vs ultrasound (Hepatology, NCT05716620) flips HCC surveillance on its head with 94.6% vs 51.4% sensitivity, and a 5-gene blood methylation panel (Clinical Epigenetics) achieves AUC 0.96 for gastric cancer screening — pointing to a near-future where modality and biology converge for organ-specific early detection.

NORCCAP 23-year follow-up — single-sigmoidoscopy screening in 98,654 adults sustains CRC incidence and mortality reduction in men two decades on (Annals of Internal Medicine), Tinengotinib Phase Ib/II — multi-kinase FGFR/JAK/VEGFR/Aurora inhibitor delivers 30.8% ORR monotherapy and 66.7% ORR in FGFR2-fusion cholangiocarcinoma progressing on prior FGFR inhibitor (Nature Communications), Non-contrast abbreviated MRI vs ultrasound for HCC surveillance — AMRI sensitivity 94.6% vs US 51.4% in 614 paired exams of cirrhotic patients (Hepatology), ASCO Educational Book — Promising new platforms and targets in gastroesophageal cancers, mapping claudin18.2, MET, TROP2, ADCs, bispecifics and CAR-T into the perioperative and advanced GEC algorithm (ASCO Educational Book), Neutrophil-driven trogocytosis in PDAC liver metastases restrains immunosuppressive macrophage polarization — intravital imaging + scRNA-seq mechanistic study reveals a new immunotherapy lever (Gastroenterology).

POD1UM-303/InterAACT-2 final analysis — retifanlimab + carbo-paclitaxel becomes the first IO-based 1L SOC for advanced squamous anal cancer, mOS 32.8 vs 22.2 mo (HR 0.75, p=0.0305) (Annals of Oncology), NORDICC 13-year colonoscopy screening RCT in 84,583 adults — CRC incidence RR 0.81 ITT / 0.55 per-protocol but mortality not statistically reduced (Lancet), NEOSUMMIT-01 3-yr follow-up of perioperative toripalimab + chemo in locally advanced gastric/GEJ cancer — 3-yr EFS 74.7% vs 56.2% (HR 0.51) and 3-yr OS 81.3% vs 72.2% (HR 0.45) (J Clin Oncol), Mosperafenib paradox-breaker BRAF inhibitor Phase Ia/b in V600E solid tumors (n=80, 63 CRC) — ORR 24.2%, CRC mPFS 6.4 mo with sustained ≥90% pERK inhibition (J Clin Oncol), C-cubed Phase 3 in Japan — sequential vs upfront oxaliplatin in 1L mCRC delivers identical mOS (27.2 vs 27.4 mo, HR 1.00) but lower early treatment burden (Communications Medicine).

Daraxonrasib first-in-class RAS(ON) inhibitor — full Phase 1-2 results land in NEJM (Wolpin et al., n=168 PDAC; 2L G12 mut ORR 35%, mOS 13.1 mo) on the heels of positive Phase 3 RASolute 302 (OS 13.2 vs 6.7 mo, HR 0.40), Perioperative NALIRIFOX nITRO Phase II long-term — mOS 32 mo ITT, 48 mo resected, TNF-α and germline DDR variants stratify outcomes (ESMO Open), SILENSES Phase II expansion of sintilimab+lenvatinib conversion → surgery in unresectable HCC — 56% conversion, 5-yr OS 73.9% in resected (Signal Transduction & Targeted Therapy), Integrated perioperative host-response optimization Phase III RCT in low rectal cancer — 24-mo DFS 92.8% vs 77.3%, OS 95.9% vs 83.5% (HR 0.39) (Surgery), BSA-adjusted bevacizumab dosing in Atezo/Bev for HCC (n=1507) — Target BBI 106–121% yields mPFS 10.3 vs 6.5 mo, mOS 24.9 vs 19.2 mo (Hepatology).

RESET-C Phase II in JCO — single-cycle neoadjuvant pembrolizumab in stage I-III dMMR colon cancer (n=85, Denmark): pCR 44%, MPR 57%, 1-year DFS 96%, 0 recurrences, only 11% G3 AEs (Gögenur et al., J Clin Oncol May 5, 2026), Daraxonrasib + GnP first-line metastatic PDAC GI-102 Phase 1/2 — ORR 58%, 6-mo PFS 84%, 6-mo OS 90% (Wolpin/Revolution Medicines, AACR 2026 late-breaking), Matched targeted therapy in advanced BTC — global cohort n=1049 (Mayo + Duke + NCC East + SCRUM-Japan), mOS 23.3 vs 14.7 mo HR 0.57, p<0.0001 (NPJ Precision Oncology), Integrated DNA + RNA profiling in cholangiocarcinoma (n=62) — KRAS-TP53 co-mutation drives 25-month OS gap, Mesenchymal subtype shorter PFS (BMC Cancer), Senescent endothelial-derived extracellular vesicles drive neoadjuvant chemoresistance in CRC via GPX4 transfer (Communications Biology, n=77).

Lancet Oncology trio models 17 cancers across 200 countries 1990–2050 — 6 GI sites, 31.5% of cancers die undiagnosed globally, scaling diagnostic/imaging workforce projected to cut cancer mortality 7.6% (Ward et al., Lancet Oncology), Cancer Discovery May cover from the Tuveson lab shows myofibroblasts induce sympathetic neuroplasticity in the PDAC precancer ecosystem (Cancer Discovery), HGCSG 1903 Phase II ramucirumab + docetaxel 2L AGC ORR 25.7% mPFS 3.1 mo mOS 11.5 mo (Gastric Cancer), COLOSOTO/PRODIGE 107 Phase II trial design — sotorasib + panitumumab + 5-FU in frail/elderly unresectable KRAS G12C mCRC (Dig Liver Dis), ENO2-MIF axis drives M2 macrophage polarization in CRC liver mets, pyrithioxin reduces metastatic burden preclinically (Signal Transduction and Targeted Therapy).

Two paired Lancet Oncology multisociety Delphi consensus papers standardize liver tumor thermal ablation — first international margin assessment framework (A0/A1/A2) and procedural-practice standards including a >100-case credentialing threshold, TNT + sintilimab + IL-2 yields 42.4% pCR in MSS/pMMR locally advanced rectal cancer Phase II (Sig Transduct Target Ther), Bayesian network meta-analysis of 48 RCTs (34,106 patients) ranks 5 commercial AI colonoscopy systems with EndoAngel best for ADR (OR 1.84, Eur J Gastroenterol Hepatol), and a ctDNA-guided framework for stopping ICIs in MSI-H/dMMR mCRC — early discontinuation (<2y) in responders shows no PFS/OS penalty, ctDNA-negative status (~80%) signals very low relapse risk (ESMO Gastrointestinal Oncology).

FDA 'safe to proceed' letter authorizing an Expanded Access Program for daraxonrasib in previously treated metastatic PDAC (Revolution Medicines), long-term update of maintenance rucaparib in BRCA1/2 or PALB2-mutant PDAC (JAMA Oncology), first phase I of the c-Met ADC telisotuzumab adizutecan (ABBV-400) in late-line mCRC (JCO), NEJM Clinical Practice review on Barrett's esophagus, and ASCO 2026 Educational Book on immunotherapy in localized CRC.

Early-onset CRC exposome risk factors (Nature Medicine), EORTC-ESTRO OligoCare Delphi consensus on metastases-directed therapy endpoints (Lancet Oncology), ERAS-0015 pan-RAS inhibitor delivers 40% ORR in 2L KRAS G12X PDAC (Erasca/OncLive), Fruquintinib + TAS-102 ± SBRT yields mPFS 8.6 mo in 3L+ mCRC Phase II (Cancer Medicine), HAIC + regorafenib + sintilimab doubles OS vs regorafenib alone in MSS/pMMR CRC liver mets (Cancer Medicine).

RAS-GTP inhibition (daraxonrasib) extends to KRAS-mutant cholangiocarcinoma with clinical responses (Cancer Cell), FDA Priority Review for zanidatamab + chemo ± tislelizumab in 1L HER2+ GEA mOS 26.4 mo HERIZON-GEA-01 (FDA/Press Release), SPARK agentic AI cancer pathology across 5400+ patients incl. CRC (Nature Medicine), REDMOD AI detects occult pancreatic cancer 475 days pre-diagnosis AUC 0.82 (Gut), Intestinal metaplasia confirmed as the only precursor to esophageal adenocarcinoma (Nature Medicine)

PI3Kγ/STING dual targeting overcomes immune suppression in PDAC (Nature Cancer), global CRC burden and early-onset trends (Nat Rev Clin Oncol), JOSD1 metabolic-immune axis in HCC (Gut), TGM2-mediated ferroptosis resistance in gastric cancer (Cell Discovery), MARCO-driven immunosuppression in cholangiocarcinoma (STTT)

Lenvatinib + PD-1 benefits GC with abundant immunosuppressive macrophages EPOC1706 correlative (Cancer Immunology Research), CAFs regulate DNA repair in PDAC through NDRG1-mediated R-loop processing Nature Cell Biology, CCNE1 gain = lethal outcome + immune desert in 1273 gastric cancer patients across 6 cohorts (British Journal of Cancer), GPR34 in damage-associated macrophages enhances anti-tumor immunity with surufatinib in PDAC (Signal Transduction and Targeted Therapy), Site-specific genomic markers predict PD-1 response in gastric/GEJ cancer C-CAT registry 912 patients (BioDrugs)

Adequate LND improves OS in esophageal cancer pCR after neoadjuvant HR 0.70 meta-analysis (Annals of Surgical Oncology), Pulmonary mets after PDAC surgery mOS 30 mo vs liver 13 mo prognostic hierarchy (Annals of Surgical Oncology), Perioperative chemo completion HR 0.20 for 1-year OS after total gastrectomy (World J Surg Oncol), EOCRC vs LOCRC 5-year survival in 92K patients with distinct prognostic profiles (J Gastroenterol Hepatol), SLC1A3 aspartate transporter promotes CRC via MDM2-p53 and M2 macrophage polarization (Cancer Science)

MAYA trial spatial immune profiling predicts chemo-IO response in MSS mCRC (Nature Communications), 5-gene liquid biopsy methylation panel AUC 0.96 for gastric cancer screening (Clinical Epigenetics), TUDCA bile acid drives gemcitabine resistance via MAPK in PDAC (Cell Mol Life Sci), AQP1 methylation signature independently predicts CCA prognosis HR 0.32 (Scientific Reports), ATOX1-targeted cuproptosis nanogel overcomes TACE refractoriness in HCC (J Nanobiotechnology)

NP137 netrin1 antibody + mFOLFIRINOX mOS 16.4 mo in locally advanced PDAC with 23% conversion surgery (Nature), HAI oxaliplatin doubles hepatic RFS after ≥4 CRLM resection in randomized Phase II (JCO), Neoadjuvant toripalimab + CapeOX 25% pCR in EBV+ gastric cancer (Nature Communications), Consolidative camrelizumab 3-year PFS 62.5% in unresectable ESCC (IJROBP), Glissonian vs hilar dissection RCT shows shorter operative time for laparoscopic hepatectomy in HCC (British Journal of Cancer)

HER2-targeted neoadjuvant therapy 75% ORR in early rectal cancer with organ preservation (AACR 2026), BBO-11818 pan-KRAS inhibitor FDA Fast Track in PDAC (FDA/NCT06917079), Pfizer PD-1×VEGF bispecific Phase 3 in 1L mCRC (NCT07222800), Ultima Genomics ppmSeq WGS-based MRD in CRC (AACR 2026), PROACTIF Y90 radioembolization mOS 21.8 mo in HCC (EClinicalMedicine)

Zolbetuximab + FOLFOX + nivolumab CLDN18.2+ gastric cancer mPFS 18 mo (Nature Medicine), Givastomig CLDN18.2 x 4-1BB ORR 77% FDA accelerated path (Phase 1b), Lancet Commission on global HCC burden (Lancet), Amivantamab + chemo durable 1L responses in WT mCRC (OrigAMI-1), Pelareorep FDA Fast Track KRAS-mut MSS mCRC

Autogene cevumeran mRNA vaccine 87.5% PDAC responders alive at 6 years (AACR 2026), Daraxonrasib 1L mPDAC ORR 58% combo + RASolute 303 enrolling (AACR 2026), NCCN gastric cancer v2.2026 durvalumab + tislelizumab (Guidelines), DYNAMIC-III ctDNA-guided adjuvant stage III colon cancer (Nature Medicine), BOT/BAL in treatment-refractory HCC (AACR)

ALASCCA aspirin halves recurrence in PI3K-altered CRC (NEJM), T-DXd real-world OS in HER2+ mCRC (AACR 2026), VS-7375 KRAS G12D ORR 52% in PDAC (AACR 2026), RZ-001 RNA-editing in HCC (AACR 2026), Early-onset CRC plenary (AACR 2026)

Bezuclastinib NDA for GIST PEAK Phase III (FDA), VCN-01 VIRAGE oncolytic virus in mPDAC (AACR 2026), Elisrasib next-gen KRAS G12C 89% ORR in CRC (AACR 2026), BOT+BAL 1L MSS mCRC (AACR 2026), STC-1010 first-in-human MSS mCRC (AACR 2026)

Romiplostim RECITE Phase III for CIT in GI cancers (NEJM), Elraglusib doubles 1-year survival in mPDAC (Nature Medicine), ESMO 2026 mCRC Guideline update (Annals of Oncology), Daraxonrasib FDA BTD for KRAS G12X PDAC (FDA), Givastomig accelerated approval pathway gastric cancer (FDA)

RASolute 302 daraxonrasib OS in PDAC (Press Release), BREAKWATER full FDA approval BRAF mCRC (FDA), AMPLIFY-201 mKRAS vaccine (Nature Medicine), EMERALD-3 IO+TACE in HCC (AstraZeneca), Optune Pax FDA approval LAPC (FDA)

RASolute 302 daraxonrasib OS in PDAC (Press Release), EMERALD-3 IO+TACE in HCC (AstraZeneca), Tinengotinib in CCA (Lancet GI Hepatol), MATTERHORN durvalumab EU approval (AstraZeneca), Lirafugratinib Priority Review CCA (FDA)

TIGIT+PD-1 dual blockade in gastric/GEJ cancer (Nature Medicine), GRAPE AI gastric cancer screening (Nature Medicine), Setidegrasib KRAS G12D degrader in PDAC (NEJM), TOPGEAR perioperative CRT in gastric cancer (NEJM), ctDNA predicts ICI outcomes in mCRC (SAMCO-PRODIGE 54)

ATOMIC trial adjuvant IO in dMMR stage III colon cancer (NEJM), BREAKWATER encorafenib/cetuximab in BRAF V600E mCRC (NEJM), Setidegrasib KRAS G12D degrader (NEJM), COMMIT triplet in dMMR mCRC (ASCO GI), HERIZON-GEA-01 zanidatamab in HER2+ GEA (Lancet)