GI Oncology Daily Digest

Phase II randomized EXTEND trial across 6 tumor-histology baskets (n=334 per protocol) tested adding metastasis-directed therapy (98% radiotherapy) to standard of care in oligometastatic solid tumors. Overall PFS HR was 0.54 (95% CI 0.41–0.72, p<0.001). The pancreas histology basket independently met its PFS-superiority threshold — the first prospective Phase II signal that oligometastatic PDAC is a treatable category rather than a statistical mirage. ctDNA clearance at 3 months post-enrollment correlated with improved survival, and correlative work identified an immune-activation signature in MDT-benefiting baskets.

Individual patient data pooled analysis from 4,913 hepatocellular carcinoma patients treated with external beam radiation therapy (median follow-up 5.0 years) — by far the largest dataset of radiation in HCC ever assembled. Median OS reached 6.8 years in BCLC-0 disease and 4.6 years in BCLC-A; treatment-naive BCLC-A patients had a median OS of 5.4 years. OS outcomes were comparable to surgical resection and thermal ablation cohorts. Ablative dose and more recent treatment year were independently associated with reduced mortality, supporting the case to formally integrate EBRT into the BCLC treatment algorithm — a point the companion JCO editorial (Dutta SW et al., DOI 10.1200/JCO-26-00521) makes explicitly.

Systematic review and meta-analysis of 768 perihilar cholangiocarcinoma patients across 6 studies — 265 underwent protocol-based neoadjuvant selection followed by liver transplantation, 503 underwent liver resection. Liver transplantation was associated with significantly higher 5-year OS, significantly higher 5-year DFS, and a higher R0 resection rate, with no difference in 30-day postoperative mortality. The data are confounded by substantial selection bias (transplant cohorts are pre-filtered by neoadjuvant chemo/RT response), but for patients who clear the neoadjuvant screen, the Mayo-style LT pathway continues to outperform resection.

First-in-human Phase 1 of TQB2102, a HER2 biparatopic antibody-drug conjugate engaging both HER2 ECD2 and ECD4 with a topoisomerase-I-inhibitor payload. Among 195 patients with HER2-expressing solid tumors, ORR was 38.7% in HER2+ CRC (n=37), 40.0% in HER2+ G/GEJ (n=37), 47.2% in HER2-low metastatic breast cancer, and 52.4% in HER2+ MBC. RP2D was 6.0 and 7.5 mg/kg Q3W. Safety was favorable for an ADC of this class — ILD occurred in only 0.5%, with grade ≥3 neutropenia at 23.2%. A Phase 3 in HER2-low MBC has been initiated; the CRC and G/GEJ signals justify a confirmatory program in GI.

In vivo CRISPR/Cas9 screen in a CMT93 murine MSS-CRC model identifies ARID3B as a key negative regulator of CD8+ T-cell tumor infiltration and antitumor function. Genetic ablation of Arid3b in CD8+ T cells dramatically increased intratumoral T-cell accumulation and produced robust tumor control. Mechanistically, ARID3B loss upregulates RUNX3, driving a tissue-resident-memory-like phenotype and effector function; Runx3 co-deletion abolishes the benefit, confirming a RUNX3-dependent axis. Targeting ARID3B is a plausible strategy to reshape the MSS-CRC microenvironment and sensitize it to checkpoint inhibitors.