GI Oncology Daily Digest

April 21, 2026 — AACR 2026 Week — Day 5
Curated by Dr. Allan Pereira — Moffitt Cancer Center

Top 5 Papers

#1
ALASCCA Phase III: Low-Dose Aspirin Halves Recurrence in PI3K-Altered Localized Colorectal Cancer
Source: NEJM / ALASCCA Investigators  |  Authors: ALASCCA Investigators (Sweden, Norway, Denmark, Finland)  |  Published: April 2026
Score: 15/20 — NEJM (10) + Phase III RCT (+3) + biomarker-guided adjuvant therapy (+2)
The ALASCCA trial, a double-blind, randomized Phase III trial across 33 hospitals in Sweden, Norway, Denmark, and Finland, randomized over 3,500 patients with stage I–III colorectal cancer harboring somatic PI3K pathway alterations (PIK3CA, PIK3R1, PTEN) to aspirin 160 mg daily or placebo for 3 years. In patients with PIK3CA hotspot mutations (exon 9 or 20), the 3-year recurrence rate was 7.7% with aspirin versus 14.1% with placebo (HR 0.49; 95% CI 0.24–0.98; p=0.04). Similar benefit was observed in patients with other PI3K pathway alterations (HR 0.42; 95% CI 0.21–0.83). This is the first randomized trial to demonstrate biomarker-guided adjuvant benefit of aspirin in colorectal cancer, potentially establishing a new precision medicine standard.
Post angle: ALASCCA Phase III in NEJM: Aspirin 160mg daily cuts CRC recurrence by 51% in PI3K-altered patients (HR 0.49, p=0.04). First biomarker-guided adjuvant aspirin trial. Precision prevention at its best. #CRC #PrecisionMedicine #NEJM
#2
Trastuzumab Deruxtecan Real-World Overall Survival in HER2-Amplified MSS Metastatic Colorectal Cancer (AACR 2026)
Source: AACR 2026 Minisymposium / Roswell Park  |  Authors: Roswell Park Comprehensive Cancer Center  |  Published: April 19, 2026
Score: 10/20 — AACR minisymposium (7) + large real-world dataset (+1) + survival benefit (+2)
Roswell Park investigators presented real-world data from 11,112 patients (9,135 standard chemotherapy; 1,977 trastuzumab deruxtecan) with HER2-amplified microsatellite stable (MSS) metastatic colorectal cancer at AACR 2026 (Abstract 1303). While 1-year OS was similar between groups, T-DXd showed a clear long-term advantage at 5 years: 58% OS rate versus 49% with standard chemotherapy. The data support earlier use of T-DXd in HER2-positive mCRC rather than reserving it for later lines of therapy. This is the largest real-world study confirming the clinical trial benefit of T-DXd in this molecular subgroup.
Post angle: AACR 2026 Minisymposium: T-DXd real-world data in HER2+ MSS mCRC (n=11,112). 5-year OS 58% vs 49% with standard chemo. Largest RWD study supports earlier use of T-DXd. #CRC #HER2 #ADC #AACR2026
#3
VS-7375: Oral KRAS G12D Dual ON/OFF Inhibitor Shows 52% ORR and 100% DCR in Pancreatic Cancer
Source: AACR 2026 / Verastem Oncology  |  Authors: Verastem Oncology / GenFleet Therapeutics  |  Published: April 2026
Score: 10/20 — AACR presentation (6) + Phase 1/2 PDAC data (+2) + FDA Fast Track (+1) + novel dual mechanism (+1)
Verastem Oncology and partner GenFleet presented updated Phase 1/2 data for VS-7375, an oral selective KRAS G12D dual ON/OFF inhibitor, in KRAS G12D-mutated solid tumors at AACR 2026. Among 23 efficacy-evaluable patients with pancreatic ductal adenocarcinoma, the confirmed ORR was 52% (90% CI 34%–70%) and disease control rate was 100%. No dose-limiting toxicities were observed. VS-7375 has FDA Fast Track Designation for KRAS G12D-mutated PDAC in both first-line and previously treated settings. The dual ON/OFF mechanism targeting both active and inactive KRAS G12D states distinguishes VS-7375 from ON-only inhibitors and may provide deeper, more sustained responses.
Post angle: AACR 2026: VS-7375, oral KRAS G12D dual ON/OFF inhibitor. • ORR 52%, DCR 100% in PDAC (n=23) • No DLTs • FDA Fast Track for 1L and 2L+ PDAC Targets both active AND inactive KRAS G12D. #PDAC #KRASG12D #AACR2026
#4
RZ-001: First RNA-Editing Therapy Shows ORR 38.5% in Hepatocellular Carcinoma Combined with Atezo/Bev (AACR 2026 Oral)
Source: AACR 2026 Oral / Rznomics  |  Authors: Kim YJ et al. (Seoul National University Hospital)  |  Published: April 19, 2026
Score: 9/20 — AACR oral presentation (7) + first-in-class RNA-editing therapy (+1) + HCC relevance (+1)
Rznomics presented interim data from the Phase 1/2 trial of RZ-001, a first-in-class trans-splicing ribozyme-based RNA-editing therapy, combined with atezolizumab and bevacizumab in treatment-naive hepatocellular carcinoma patients ineligible for or refractory to TACE at AACR 2026 (oral presentation, April 19). The combination achieved a confirmed ORR of 38.5% (unconfirmed 46.2%) by RECIST v1.1, with a favorable safety profile. RZ-001 has both FDA Orphan Drug and Fast Track Designations for HCC. This represents the first clinical demonstration of RNA-editing therapy in solid tumors and introduces a novel modality for liver cancer treatment.
Post angle: AACR 2026 Oral: RZ-001, first RNA-editing therapy in cancer. • ORR 38.5% (confirmed) in 1L HCC • Combined with atezo/bev • FDA Orphan Drug + Fast Track Novel trans-splicing ribozyme platform. RNA editing enters oncology. #HCC #LiverCancer #AACR2026
#5
AACR 2026 Plenary: Early-Onset Colorectal Cancer Now Leading Cancer Death in Adults Under 50
Source: AACR 2026 Plenary / Mass General Brigham  |  Authors: Chan AT (Mass General Brigham Cancer Institute)  |  Published: April 21, 2026
Score: 9/20 — AACR plenary session (8) + direct CRC relevance (+1)
In today's AACR 2026 plenary session "Early-onset Cancers: Why Are More Young Adults Getting Cancer?", Andrew T. Chan, MD, MPH, Director of Cancer Epidemiology at Mass General Brigham, presented "Early-onset colorectal cancer: Advancing correlation to causation to prevention." CRC has become the leading cause of cancer death in US adults under age 50, with incidence rising sharply since the 1990s. Chan reviewed established risk factors (obesity, Western diet, sedentary lifestyle, antibiotic use in early life), emerging microbiome-mediated mechanisms, and strategies for moving from epidemiologic correlation to causal understanding and prevention. The session highlighted the urgent need for personalized screening approaches in younger populations.
Post angle: AACR 2026 Plenary (TODAY): Early-onset CRC is now the #1 cancer killer in US adults under 50. Andrew Chan (MGH) reviewed: • Rising incidence since the 1990s • Risk factors: diet, obesity, microbiome • Path from correlation to prevention We must act. #EarlyOnsetCRC #AACR2026 #CRC

Additional Papers of Interest

  1. H. pylori Screen-and-Treat Programs for Gastric Cancer Prevention — IARC Working Group Report
    NEJM / IARC Working Group — H. pylori eradication reduces gastric cancer risk (RR 0.64). NNT 228. Recommends population-based screening in intermediate-to-high-risk areas (≥10 cases/100,000).
  2. Zoldonrasib KRAS G12D Plenary: ORR 52%, mPFS 11.1 mo in NSCLC; FDA Breakthrough Therapy
    AACR 2026 Plenary / Revolution Medicines — RAS(ON) G12D inhibitor zoldonrasib: ORR 52%, mPFS 11.1 mo in NSCLC. KRAS G12D is the most common PDAC mutation (40%), making this pipeline highly GI-relevant.
  3. GLP-1 Receptor Agonists Reduce Colorectal Cancer Risk by 36% Versus Aspirin
    ASCO GI 2026 — Real-world study of 281,656 patients: GLP-1 RAs (semaglutide, liraglutide, dulaglutide) reduced CRC risk by 36% vs aspirin regardless of obesity/diabetes status.
  4. Muzastotug Combination Shows 66.7% ORR in Hepatocellular Carcinoma (AACR 2026)
    AACR 2026 Poster / Adagene — Muzastotug backbone combination therapy demonstrates 66.7% ORR in HCC, highlighting masked anti-CTLA-4 as a potential new HCC approach.
  5. UCLA: KRAS G12D Inhibition Boosts mRNA Immunotherapy in Pancreatic Cancer (Preclinical)
    AACR 2026 / UCLA — Preclinical data showing KRAS G12D targeted inhibition enhances tumor immune recognition and mRNA vaccine responses in PDAC models.
  6. Cardiff Oncology: Onvansertib PLK1 Inhibitor + HER2-ADC Preclinical Data in CRC (AACR 2026)
    AACR 2026 Poster / Cardiff Oncology — PLK1 inhibitor onvansertib combined with HER2-targeted ADC shows enhanced antitumor activity in CRC preclinical models.
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