📬 GI Cancer Intelligence Digest — Week 2026-W33
BEACON-HCC replaces BCLC-style allocation for hepatocellular carcinoma, SOLARIS shows high-dose vitamin D3 adds nothing in metastatic colorectal cancer, and PICC-2, ARISTOTLE, TORCH, COMPETE and DESTINY-PanTumor02 all report across GI oncology.
⚡ TL;DR
📄 Publications
- Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703). — 455 patients with previously untreated mCRC randomized
🐦 Twitter / 🦋 Bluesky
- BEACON-HCC: a new multidisciplinary treatment allocation framework for hepatocellular carcinoma published in Hepatology — BEACON-HCC is a new HCC treatment allocation system developed by the HCC LIVE consortium, and VP1/2 is no longer considered advanced disease
- PICC-2: adding celecoxib to neoadjuvant toripalimab raises pathological complete response in dMMR/MSI-H colorectal cancer — Pathological complete response increased from 69% to 89% with the addition of celecoxib, an absolute gain of 19 percentage points (P=0.014)
- KRAS inhibition synergizes with CTLA-4 blockade in preclinical pancreatic cancer — Oncogenic KRAS targeting with MRTX1133 or daraxonrasib specifically synergizes with anti-CTLA4 to promote anti-tumor immunity in pancreatic cancer
- Review of precision oncology in MSS colorectal cancer beyond RAS and BRAF circulates widely — The review covers precision oncology beyond RAS/RAF in MSS colorectal cancer including ADCs and bispecifics, TME-targeted strategies, CAR-T and DDR approaches, and spatial profiling with AI
- Update: ARISTOTLE discussion widens as clinicians debate whether irinotecan-containing regimens belong in rectal cancer at all — 36-month DFS was 68% vs 67% with HR 0.91 (95% CI 0.68-1.23; P=0.54), no OS benefit (HR 0.97), and grade ≥3 toxicity 78% vs 52%
Full details below ↓
📄 What's Being Published
Phase I Trial of GPC3-Targeted TCR Fusion Construct, CT0180, in patients with Advanced Hepatocellular Carcinoma. — Sun Xuqi et al., Clin Cancer Res
Seven patients received 15 infusions across four dose levels (1×10⁷, 3×10⁷, 1×10⁸, and 3×10⁸ cells). Cytokine release syndrome occurred in 85.7% of patients, all grade 1, with no dose-limiting toxicities or immune effector cell-associated neurotoxicity; the objective response rate was 28.6% and disease control rate 71.4%. Median progression-free and overall survival were 7.6 and 11.6 months, respectively.
Clinical bottom line: The full CT0180 report adds efficacy detail — a 28.6% response rate and 11.6-month median overall survival — to the previously noted grade 1 cytokine release syndrome signal, keeping GPC3-directed TCR fusion constructs a credible later-line option to test in hepatocellular carcinoma.
Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703). — Ng Kimmie et al., JAMA
This double-blind phase 3 randomized clinical trial enrolled 455 patients with previously untreated metastatic colorectal cancer. Median PFS for high-dose vitamin D3 (n=228) was 11.8 months (95% CI, 10.3–13.3) versus 10.3 months (95% CI, 9.4–12.2) for standard-dose vitamin D3 (n=227), with a 1-sided log-rank P of .25. There were no significant differences in objective response rate (51% [95% CI, 44%–58%] vs 44% [95% CI, 37%–50%]; P=.12) or overall survival (median 25.6 vs 27.0 months; 1-sided log-rank P=.66).
Clinical bottom line: High-dose vitamin D3 should not be added to first-line chemotherapy plus bevacizumab in metastatic colorectal cancer: the phase 3 SOLARIS trial found no gain in progression-free survival, response rate, or overall survival.
🗣️ What People Were Discussing This Week
How these are chosen: filtered for clinical relevance, grouped by the new development discussed, then ordered by engagement (bookmarks and reposts).
BEACON-HCC: a new multidisciplinary treatment allocation framework for hepatocellular carcinoma published in Hepatology
BEACON-HCC is a new HCC treatment allocation system developed by the HCC LIVE consortium that differs from BCLC in multiple respects; most notably, VP1/2 portal vein involvement is no longer classified as advanced disease. The framework explicitly incorporates SBRT and Y90 based on current evidence, reflecting contemporary multidisciplinary practice. AASLD describes it as a landmark expert consensus marking the biggest shift in liver cancer treatment in decades. HPB and transplant teams are actively asking whether selected Vp1–2 patients still have a pathway to curative-intent treatment under the new allocation system.
Discussed by: @MarkYarchoan, @MarkYarchoan, @NiuSanford, @DrElkhoueiry, @MikelPrieto4, @AASLDtweets
PICC-2: adding celecoxib to neoadjuvant toripalimab raises pathological complete response in dMMR/MSI-H colorectal cancer
The PICC-2 trial explored whether blocking the COX-2/PGE₂ pathway could reduce immune suppression in the tumor microenvironment and enhance PD-1 blockade activity in dMMR/MSI-H locally advanced colorectal cancer. The primary result was a pathological complete response increase from 69% to 89% — an absolute improvement of 19 percentage points (P=0.014). Safety was similar between groups with no grade 4/5 treatment-related adverse events, lending the finding a favorable risk-benefit profile at this phase of investigation.
Discussed by: @ChandrakanthMv, @ChandrakanthMv
KRAS inhibition synergizes with CTLA-4 blockade in preclinical pancreatic cancer
A study published in Nature from the Kalluri Lab dissects the mechanism behind why CTLA-4 blockade is effective when combined with a KRAS inhibitor in pancreatic cancer. Oncogenic KRAS targeting with MRTX1133 or daraxonrasib specifically synergizes with anti-CTLA-4 to promote anti-tumor immunity. The findings, shared by surgical oncology voices, position CTLA-4 rather than PD-1 blockade as the logical immunotherapy partner for the next generation of RAS inhibitor combinations in pancreatic cancer.
Discussed by: @OncoAlert, @EladSharonMD
Review of precision oncology in MSS colorectal cancer beyond RAS and BRAF circulates widely
A widely circulated review covers precision oncology beyond RAS/RAF in pMMR/MSS colorectal cancer, encompassing ADCs and bispecific antibodies, TME-targeted strategies, CAR-T and DDR approaches, and spatial profiling integrated with AI-based multiomic profiling. The breadth of approaches under review reflects a field that, as one clinician notes, has not had a game-changing drug that is broadly applicable in colorectal cancer in nearly 20 years. The debate centers on which strategy — ADCs, bispecifics, or cellular therapy — is closest to a randomized readout.
Discussed by: @ronanhsieh, @OncoAlert
Update: ARISTOTLE discussion widens as clinicians debate whether irinotecan-containing regimens belong in rectal cancer at all
ARISTOTLE reported 36-month DFS of 68% vs 67% (HR 0.91, 95% CI 0.68–1.23; P=0.54), no OS benefit (HR 0.97), and substantially higher grade ≥3 toxicity at 78% vs 52%, including diarrhoea 14% vs 4% and neutropenia 10% vs 1%. One commentator argues XELIRI/CAPIRI should be banned as a chemotherapy regimen in colorectal cancer, while others contend that for patients requiring treatment escalation, total neoadjuvant therapy remains the evidence-based strategy rather than concurrent irinotecan. A separate AI analysis introduces a potential biomarker dimension, suggesting patients with high tumor cell density had improved survival with irinotecan-intensified chemoradiotherapy versus those with low density.
Discussed by: @DrRishabhOnco, @ChandrakanthMv, @jgong15, @SammyShaya, @ASCOPost
Update: TORCH draws pushback on its design even as it reports a survival gain for TACE plus thermal ablation
TORCH reported that sequential TACE and thermal ablation improved survival compared with TACE alone in liver-confined unresectable HCC, with PFS 17.7 vs 7.3 months and OS 88.6 vs 35.1 months (HR 0.50) in 241 patients. One radiation oncologist disputes the experimental premise, noting that TACE achieved an mRECIST ORR of only 57% before residual tumor was ablated, and questions whether attributing benefit to the combination is justified when the control arm received deliberately incomplete locoregional treatment. The debate turns on whether the survival signal is a property of the combination strategy or an artefact of trial design.
Discussed by: @ArndtVogel, @NiuSanford, @ModernMediks
DESTINY-PanTumor02 subgroup analysis: trastuzumab deruxtecan is active in HER2 IHC 3+ biliary tract cancer but not pancreatic
In the DESTINY-PanTumor02 subgroup analysis, biliary tract cancer showed an ORR of 22.0%, rising to 56% in HER2 IHC 3+ disease, with a median OS of 7 months. In pancreatic cancer, the response rate was only 4%, underscoring the divergence in HER2-driven activity across upper GI tumor types. Commentators stress upfront NGS with IHC for HER2 as the key testing strategy to identify patients with biliary tract cancer who may derive meaningful benefit.
Discussed by: @ArndtVogel, @OncoAlert, @DrAllanPereira
Update: Cancer Cell editorial accompanies the colorectal micrometastasis spatial mapping paper
An editorial in Cancer Cell accompanies a paper mapping cellular and molecular neighborhoods of colorectal cancer micro- and macro-metastases, framing micrometastases as the seeds of relapse. Related work on ctDNA and minimal residual disease after colorectal resection is being presented at the STOP cancer summit. The central clinical question is whether the dormant micrometastatic niche described points toward a druggable target or only toward a more refined minimal residual disease biomarker.
Discussed by: @Aiims1742, @VivekSubbiah
Update: STELLAR 5-year data circulated again, with the durable overall survival benefit foregrounded over disease-free survival
The 5-year STELLAR trial results show that short-course radiotherapy followed by chemotherapy as total neoadjuvant therapy offers a durable overall survival benefit compared with standard long-course chemoradiotherapy in locally advanced rectal cancer; disease-free survival, distant metastasis, and locoregional recurrence were similar, with the gain concentrated in high-risk patients and post-recurrence outcomes. In the separate TNTCRT phase III (n=458), doublet-based long-course TNT significantly improved 3-year disease-free survival to 74.8% vs 66.0% (HR 0.67) in MRI-defined high-risk locally advanced rectal cancer. With an OS benefit demonstrated by STELLAR in the absence of a DFS difference, clinicians are debating which total neoadjuvant backbone to default to in high-risk disease.
Discussed by: @OncoAlert, @ChandrakanthMv
Update: COMMIT debate broadens from a positive PFS readout to whether atezolizumab belongs in MSI-H colorectal cancer
COMMIT reported HR 0.42, median PFS 24.5 vs 5.3 months, ORR 86% vs 46%, and primary progression 2.8% vs 32.4% for mFOLFOX6 plus bevacizumab plus atezolizumab versus atezolizumab alone, confirming a significant PFS improvement for the combination. However, single-agent atezolizumab reached 12-month PFS of 35% and 24-month PFS of 32%, compared with 55% and 48% for pembrolizumab in KEYNOTE-177, raising questions about the immunotherapy backbone. Other clinicians frame COMMIT as hypothesis-generating given better PFS and a higher response rate, but note there was no OS benefit and more toxicity with the combination regimen.
Discussed by: @GIMedOnc, @K_Yadavir, @GIMedOnc, @ASCOPost
Update: COMPETE circulates in the Lancet and clinicians place PRRT alongside NETTER-1 and NETTER-2 as a cornerstone in GEP-NETs
COMPETE randomized 309 patients with progressive, SSTR-positive, well-differentiated G1–2 GEP-NET; 177Lu-edotreotide nearly doubled median PFS versus everolimus at 23.9 vs 14.1 months (HR 0.67; P=.022), with ORR 22% vs 4% and fewer grade 3/4 treatment-related adverse events. Overall survival was not significantly different at 63.4 vs 58.7 months, with OS data described as still immature. Positioned alongside NETTER-1 and NETTER-2, COMPETE strengthens the view that PRRT is no longer only a later-line therapy but a cornerstone of treatment across multiple stages of advanced SSTR-positive NET, renewing debate about any remaining first-line role for everolimus in this setting.
Discussed by: @ChandrakanthMv, @ChandrakanthMv, @OncLive
Update: first-in-human mutant KRAS vaccine for pancreatic cancer interception keeps drawing surgical and clinical comment
A KRAS-specific T-cell response was observed in 90% of participants, persisting for up to 2 years, with no participants developing pancreatic cancer during a median follow-up of 16.5 months. The durable immunologic signal continues to attract comment from surgical and clinical oncologists, though the central question remains whether immune interception in high-risk pancreatic cohorts is ready for a randomized prevention endpoint or only for longer immunologic follow-up.
Discussed by: @Gio_Marchegiani, @MedChemExpress
SOLARIS phase III: high-dose vitamin D3 fails to improve outcomes in first-line metastatic colorectal cancer
In first-line metastatic colorectal cancer, high-dose versus standard-dose vitamin D3 added to chemotherapy plus bevacizumab yielded median PFS 11.8 vs 10.3 months, ORR 51% vs 44%, and OS 25.6 vs 27.0 months — none statistically significant. Adding high-dose vitamin D3 to chemotherapy plus bevacizumab did not improve progression-free survival versus standard-dose vitamin D3. Investigators note biological evidence that vitamin D changes the tumor microenvironment in stage I–3 colon cancer, and lead author Kimmie Ng has discussed whether those microenvironmental changes, potentially linked to anti-cancer activity, justify continued investigation in earlier-stage disease.
Discussed by: @OncoAlert, @JAMA_current, @EladSharonMD, @jama.com
Chinese guidelines for HER2-targeted therapy in gastric and gastroesophageal junction adenocarcinoma, 2025 edition
Chinese guidelines for HER2-targeted therapy in gastric and gastroesophageal junction adenocarcinoma were released as a 2025 edition, codifying current standards for HER2-directed treatment in this disease. Kohei Shitara has separately addressed challenges and opportunities for HER2-targeted agents in metastatic esophagogastric cancer, including areas where further research is needed. Clinicians are comparing the extent to which the new Chinese guidance aligns with Western practice in gastroesophageal junction adenocarcinoma.
Discussed by: @OncoAlert, @VJOncology
AXL as a resistance node to KRAS inhibition in pancreatic cancer preprint
A new preprint reports that targeting AXL overcomes adaptive resistance to KRAS inhibition in KRAS-driven lung and pancreatic cancer, with authors calling for KRAS inhibitor plus AXL inhibitor combination trials to sustain responses. Early-phase data continue to show efficacy and safety signals for KRAS inhibitors in pancreatic cancer, supporting continued development of targeted approaches. AXL now joins a list of adaptive resistance nodes emerging around pancreatic KRAS inhibition, and the field is debating whether it is the most tractable target in this context.
Discussed by: @OncoAlert, @PanClawd
Update: FIND ctDNA methylation surveillance data spread beyond the trialists into wider colorectal practice debate
The FIND phase III demonstrated that ctDNA methylation-guided surveillance detected relapse 3.9 months earlier and doubled the rate of curative-intent treatment at recurrence (48.1% vs 23.6%; RR 2.03; P=0.008) in resected colorectal cancer. Curative resection of liver or lung recurrence was achieved in 42.3% vs 18.2% of patients, though mature survival data remain absent. Commentators across the colorectal oncology community are debating whether doubled curative-intent salvage is sufficient to adopt methylation surveillance before overall survival endpoints mature.
Discussed by: @jgong15, @ErulEnes, @OncoAlert
SPACE-FLOT: peritoneum is the dominant and earliest relapse site after perioperative FLOT in 2240 patients
In SPACE-FLOT (N=2240), the peritoneum was the most common relapse site at 41%, occurring earlier than nonperitoneal relapse at 9.8 vs 11.4 months, with post-recurrence survival of 4.4 vs 9.8 months. Pre- and post-treatment models predicted peritoneal relapse with AUC 0.74–0.80. Trial groups including EA2234/STOPGAP 2 are testing new treatment approaches in gastric cancer; the SPACE-FLOT prediction model data are informing discussion of whether intraperitoneal-directed strategies are justified after perioperative FLOT.
Discussed by: @OncoAlert, @eaonc
Histotripsy for liver tumors in US practice: 11.1% 30-day mortality in 972 patients prompts a warning against hype
Among 972 patients treated with histotripsy for liver tumors in US practice, 30-day mortality was 11.1%. A hepatobiliary oncologist describes the data as very concerning and warns of too much hype around the procedure, noting that patients are actively arriving at clinics asking about histotripsy as a safe treatment option. Clinicians face the practical challenge of counseling these patients against the background of a real-world mortality signal that contrasts with the procedure's public profile.
Discussed by: @ArndtVogel, @bsc_io_e
PANCprAId: histology-based AI predicts which resected pancreatic cancers benefit from mFOLFIRINOX
A histology-based AI model predicts benefit from mFOLFIRINOX versus gemcitabine in resected pancreatic ductal adenocarcinoma, validated in PRODIGE-24 with a DFS interaction P=0.003. Commentators caution that transcriptomic and histologic adjuvant selection tools — including this approach — are not yet ready for routine clinical practice and require prospective validation. The field is debating what level of prospective evidence would be needed before an AI histology score is used to choose between mFOLFIRINOX and gemcitabine after resection.
Discussed by: @ronanhsieh, @SharksJClub
FDA grants breakthrough therapy designation to olomorasib in KRAS G12C-mutant pancreatic cancer
The FDA granted breakthrough therapy designation to olomorasib monotherapy for adults with advanced pancreatic cancer harboring a KRAS G12C mutation who have received at least one prior systemic therapy, based on data from the phase 1/2 LOXO-RAS-20001 trial. Olomorasib is a next-generation KRAS G12C inhibitor designed to achieve sustained target inhibition. With daraxonrasib under NDA review and olomorasib now designated, clinicians are weighing how KRAS G12C-specific and pan-RAS inhibitors will be sequenced in pancreatic cancer.
Discussed by: @OncLive, @CancerNetwrk, @MedChemExpress, @Larvol
ACT-GI phase 2: avatrombopag corrects persistent chemotherapy-induced thrombocytopenia in GI cancers
The phase 2 ACT-GI trial showed that avatrombopag, an oral thrombopoietin receptor agonist, corrected persistent chemotherapy-induced thrombocytopenia in 70% of patients with GI cancers, with the framing that it may help patients stay on planned chemotherapy. An accompanying commentary questions whether this represents a big solution for a small problem — or a solution at all. The practical debate is whether correcting thrombocytopenia in 70% of patients is sufficient to justify routine thrombopoietin agonist use over dose modification.
Discussed by: @ASCOPost, @JCO_ASCO, @CancerNetwrk
FDA approves SimpleScreen CRC, a second blood-based colorectal cancer screening test
The FDA approved SimpleScreen CRC for adults 45 years and older at average risk of developing colorectal cancer, making it the second FDA-approved blood-based biomarker test for colorectal cancer. Based on the PREEMPT CRC study with over 48,000 participants, CRC sensitivity was 81.1%, specificity 90.4%, and advanced lesion sensitivity 13.7%. The low advanced lesion sensitivity anchors the clinical debate: whether a blood test can effectively reach the unscreened population without displacing colonoscopy in those already engaged in screening.
Discussed by: @Dr_ElvinaA, @HealioGastro, @CancerNetwrk
FDA approves zenocutuzumab for NRG1 fusion-positive cholangiocarcinoma
The FDA approved zenocutuzumab for adults with advanced, inoperable, or metastatic cholangiocarcinoma driven by an NRG1 gene fusion, offering a new targeted treatment option for patients with previously treated disease. Clinicians frame the approval alongside the role of comprehensive molecular testing to identify this patient population. The approval reframes the threshold question of whether RNA-based fusion testing should be ordered reflexively in every biliary tract cancer diagnosis.
Discussed by: @EladSharonMD, @EladSharonMD
🔥 Top Ranked Tweets
Elad Sharon @EladSharonMD
RT @MSKCancerCenter: The FDA has approved #zenocutuzumab for adults with advanced, inoperable, or metastatic cholangiocarcinoma driven by an NRG1 gene fusion.
The approval is based on a clinical trial led by MSK’s @AliSchram giving patients with limited treatment options a new choice. Learn more: https://t.co/nRgOcquClD
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Nicholas Hornstein @GIMedOnc
Hear me out.
On paper COMMIT is a "Positive" trial.
It is also a spectacular demonstration that Atezolizumab monotherapy should never be used for metastatic MSI-H CRC (we can talk about adjuvant).
COMMIT was a randomized first-line study in metastatic MSI-H/dMMR CRC.
It began as a 3-arm trial of:
• mFOLFOX6/bevacizumab (this sucks)
• atezolizumab alone
• mFOLFOX6/bevacizumab/atezolizumab
After KEYNOTE-177 changed the standard of care, the chemotherapy-only arm closed after 20 patients. The trial continued with 82 patients randomized between atezo alone and the four-drug combination.
The headline is that adding FOLFOX/bevacizumab to atezo improved PFS:
HR 0.42
Median PFS: 24.5 vs 5.3 months
ORR: 86% vs 46%
Primary progression: 2.8% vs 32.4%
The truth is Atezolizumab PALES in comparison to its contemporary PD1/PDL1 agents in this setting.
Single-agent atezo:
12-month PFS 35%
24-month PFS 32%
For comparison:
Pembrolizumab in KEYNOTE-177:
12-month PFS 55%
24-month PFS 48%
Nivolumab in CheckMate 8HW:
12-month PFS 63%
24-month PFS 56%
This is not evidence that every patient with metastatic MSI-H CRC needs chemotherapy, bevacizumab, and immunotherapy.
It is evidence that NO ONE SHOULD BE USING ATEZOLIZUMAB IN METASTATIC MSI-H CRC.
And now, drumroll please…
The only positive randomized adjuvant immunotherapy strategy in stage III dMMR colon cancer is ATOMIC:
FOLFOX + atezolizumab.
That makes COMMIT more than a roast. It raises a important question about ATOMIC.
Should we be using Atezolizumab in the adjuvant setting? Do we need to be giving chemotherapy here? Looking forward to what others make of this but this is the real question.
https://t.co/YQDkBGjBBU
@TheGutOncLab @OncoAlert @oncodaily
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MV Chandrakanth @ChandrakanthMv
TNTCRT Trial: Front-Loading Chemotherapy Improves Disease-Free Survival in High-Risk Rectal Cancer
• Phase III trial in MRI-defined high-risk locally advanced rectal cancer (n=458).
• Doublet-based long-course TNT significantly improved 3-year disease-free survival (74.8% vs 66.0%; HR 0.67).
• The benefit was driven by fewer distant metastases, while pelvic control remained essentially unchanged.
• Pathological complete response was nearly three-fold higher (26.4% vs 9.8%).
• Grade ≥3 toxicity occurred earlier with TNT, but overall treatment-related toxicity was comparable across the full treatment course.
• Overall survival has not yet reached statistical significance; longer follow-up is awaited.
Take-home: Front-loading systemic chemotherapy before surgery improves disease control primarily by reducing distant metastases, supporting TNT as an effective strategy for appropriately selected patients with high-risk locally advanced rectal cancer.
#RectalCancer #TNT #GIOncology #MedicalOncology #RadiationOncology #ASCO #ESMO #MVOnco
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Targeted Oncology @TargetedOnc
🔬 Sonesitatug vedotin, a first-in-class anti-CLDN18.2 ADC, demonstrated a statistically significant and clinically meaningful improvement in OS vs chemo in patients with 2L+ CLDN18.2-positive advanced gastric and GEJ cancers.
Read more: https://t.co/csn6BBGpMq
#GIOncology
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Journal of Clinical Oncology @JCO_ASCO
Adjuvant Chemotherapy 6 Chemoradiotherapy for Adenocarcinoma of the Pancreatic Head: Results of the Radiotherapy Random Assignment of NRG Oncology/RTOG 0848.
Read the full article. https://t.co/guC2mKNIQc
#pamcsm
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OncLive.com @OncLive
COMPETE hits its primary endpoint: ¹⁷⁷Lu-edotreotide nearly doubled median PFS vs everolimus (23.9 vs 14.1 months; HR, 0.67; P = .022) in advanced GEP-NETs, with a higher ORR (22% vs 4%) and fewer grade 3/4 TRAEs. Jonathan Strosberg, MD breaks down the phase 3 data.
Watch now: https://t.co/vKzDnbbQvj
#NeuroendocrineTumors #GEPNETs #PRRT
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OncoDaily @oncodaily
Daraxonrasib for Pancreatic Cancer: What’s Next?
In this video on #OncoDaily, Dr. Amalya Sargsyan sits down with Dr. Eileen O'Reilly , Medical Oncologist at Memorial Sloan Kettering Cancer Center and lead author of the RESOLUTE-302 trial, one of the most significant #pancreaticcancer studies presented at the 2026 #ASCO Annual Meeting.
Dr. O'Reilly discusses the groundbreaking RESOLUTE-302 Phase III trial evaluating daraxonrasib, a novel pan-RAS inhibitor, in previously treated metastatic pancreatic cancer.
The conversation explores how targeting KRAS mutations is transforming a disease long considered one of the most challenging in oncology, delivering significant improvements in overall survival, progression-free survival, response rates, and quality of life.
The discussion also covers the biology of KRAS-driven pancreatic cancer, toxicity management, future combination strategies, the role of genomic profiling, and what the next five years may hold for patients with pancreatic cancer as RAS-targeted therapies move into earlier treatment settings.
Watch the full video here: https://t.co/hW5n0ZxvKu
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OncoAlert @OncoAlert
RT @OncoAlert: Can short-course radiotherapy followed by chemotherapy deliver durable survival benefits for patients with locally advanced rectal cancer.
Article 👉 https://t.co/QkU8evLrf4
Five-Year Outcomes of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy for Locally Advanced Rectal Cancer: Updated Results of the STELLAR Trial💫
The 5-year STELLAR trial results show that short-course radiotherapy☢️ followed by chemotherapy🧪 as total neoadjuvant therapy (TNT) offers a durable overall survival benefit compared with standard long-course chemoradiotherapy in locally advanced rectal cancer.
Although disease-free survival, distant metastasis, and locoregional recurrence were similar, TNT significantly improved overall survival, particularly in high-risk patients, and outcomes after recurrence, supporting TNT as an effective alternative to conventional CRT.
@CathyEngMD
@BenWestphalen
@graokane
@NiuSanford
@AndresC27622123
@GillSharlene
@pashtoonkasi
@DrVilmaPBarcia
@Erman_Akkus
@GIMedOnc
@UOzkerim
@MarioBalsaMD
@p_ciracimd
@DraMartinezLago
@DaisukeKotani
@Aiims1742
@ARosen380
@realbowtiedoc
@KoheiShitara
@MarioBalsaMD
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Kate Sears @MedwatchKate
Top Post of the Week in #CRC:
[Quoting @GIMedOnc: Hear me out.
On paper COMMIT is a "Positive" trial.
It is also a spectacular demonstration that Atezolizumab monotherapy should never be used for metastatic MSI-H CRC (we can talk about adjuvant).
COMMIT was a randomized first-line study in metastatic MSI-H/dMMR CRC.
It began as a 3-arm trial of:
• mFOLFOX6/bevacizumab (this sucks)
• atezolizumab alone
• mFOLFOX6/bevacizumab/atezolizumab
After KEYNOTE-177 changed the standard of care, the chemotherapy-only arm closed after 20 patients. The trial continued with 82 patients randomized between atezo alone and the four-drug combination.
The headline is that adding FOLFOX/bevacizumab to atezo improved PFS:
HR 0.42
Median PFS: 24.5 vs 5.3 months
ORR: 86% vs 46%
Primary progression: 2.8% vs 32.4%
The truth is Atezolizumab PALES in comparison to its contemporary PD1/PDL1 agents in this setting.
Single-agent atezo:
12-month PFS 35%
24-month PFS 32%
For comparison:
Pembrolizumab in KEYNOTE-177:
12-month PFS 55%
24-month PFS 48%
Nivolumab in CheckMate 8HW:
12-month PFS 63%
24-month PFS 56%
This is not evidence that every patient with metastatic MSI-H CRC needs chemotherapy, bevacizumab, and immunotherapy.
It is evidence that NO ONE SHOULD BE USING ATEZOLIZUMAB IN METASTATIC MSI-H CRC.
And now, drumroll please…
The only positive randomized adjuvant immunotherapy strategy in stage III dMMR colon cancer is ATOMIC:
FOLFOX + atezolizumab.
That makes COMMIT more than a roast. It raises a important question about ATOMIC.
Should we be using Atezolizumab in the adjuvant setting? Do we need to be giving chemotherapy here? Looking forward to what others make of this but this is the real question.
https://t.co/YQDkBGjBBU
@TheGutOncLab @OncoAlert @oncodaily]
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MV Chandrakanth @ChandrakanthMv
COMPETE Trial (Lancet 2026) 🧵
• First Phase III trial to directly compare PRRT vs everolimus in advanced GEP-NET.
• Included 309 patients with progressive, SSTR-positive, well-differentiated G1–2 GEP-NET.
• PRRT significantly prolonged progression-free survival: 23.9 vs 14.1 months (HR 0.67)
• PRRT produced 5× more tumour shrinkage: 22% vs 4% response rate
• Overall survival was not significantly different: 63.4 vs 58.7 months (OS data still immature)
• Patients receiving PRRT reported better quality of life than those on everolimus.
• PRRT caused fewer severe side effects: 18% vs 40% Grade 3–4 treatment-related adverse events
• Treatment discontinuation due to toxicity was much lower with PRRT: 6% vs 23%
• Main PRRT toxicities: Lymphopenia, mild marrow suppression, rare MDS (~1%), with good renal safety using amino acid protection.
• Clinical message: For eligible patients with progressive SSTR-positive GEP-NET after prior therapy, PRRT should generally be preferred over everolimus.
#MVOnco #COMPETE #NeuroendocrineTumors #GEPNET #PRRT #Everolimus #MedicalOncology #Lancet #OncologyResearch
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Mark Yarchoan @MarkYarchoan
➡️BEACON-HCC is a new HCC treatment allocation system for #HCC, developed by @HCCLIVEConf consortium
There are MANY differences vs BCLC but perhaps most significant, VP1/2 is no longer considered "advanced disease" https://t.co/AxbqMslPc9
[Quoting @AASLDtweets: Now online in @HEP_Journal!
A new landmark, expert consensus reflects the biggest shift in #livercancer treatment in decades.
BEACON-HCC is a contemporary framework for treatment allocation in #HepatocellularCarcinoma #HCC that reflects today's rapidly evolving therapeutic landscape.
➡️ Learn more: https://t.co/pYus0mizXx]
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Journal of Clinical Oncology @JCO_ASCO
‼️ #ASCO26 simultaneous publication by Bekaii-Saab et al:
Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor-2 Rearrangement: Results From the Phase 3 FIGHT-302 Trial
Read the full article: https://t.co/4Tm3YZ9hOx
#gicsm https://t.co/Ml26XElTuZ
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AASLD @AASLDtweets
Now online in @HEP_Journal!
A new landmark, expert consensus reflects the biggest shift in #livercancer treatment in decades.
BEACON-HCC is a contemporary framework for treatment allocation in #HepatocellularCarcinoma #HCC that reflects today's rapidly evolving therapeutic landscape.
➡️ Learn more: https://t.co/pYus0mizXx
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Elad Sharon @EladSharonMD
RT @DrChoueiri: August 5 issue of @Nature:
3 foundational papers that substantially expand patient-derived 3D cancer models and show what they can add beyond traditional 2D cell lines.
1️⃣ HCMI: 665 models from 637 patients across 25 cancer types, including rare cancers and more diverse patient populations. Tumor-model genomic concordance was remarkably high (97.8%). Importantly, the work also shows where models can diverge from the original tumor—through stromal loss, clonal selection, and culture-driven epigenetic changes, some of which were reversible. These models are publicly available!
2️⃣ @sangerinstitute : 256 clinically annotated organoids across 5 cancers, with genome-wide CRISPR screens in 162. The screens uncovered dependencies that may be missed in conventional models. A nice example: KRAS dependency in colorectal cancer differed by allele—G12X tumors retained EGFR dependence, whereas Q61H did not. Treatment also reshaped dependencies, highlighting how cancer evolution can create new vulnerabilities.
3️⃣ @broadinstitute DepMap: 314 NextGen models across 10 cancers, including 147 CRISPR screens. These models reproduced tumor lineage far better than traditional cell lines—particularly striking in CNS tumors (93% vs 11%). They also uncovered context-specific dependencies in PDAC and GBM and showed something important: culture conditions themselves can change which genes appear essential (@DanaFarber_GU authors) with @boehmjesse team!
Taken together, these studies move cancer dependency mapping closer to the biology of actual human tumors. The model matters—and so does the environment in which we study it.
🔅
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Elad Sharon @EladSharonMD
RT @MarkYarchoan: 1/6 Published today in @HEP_Journal @docamitgs
https://t.co/59fmikB7Oa
➡️BEACON-HCC, a new treatment allocation system for #HCC, developed by @HCCLIVEConf consortium
AASLD Statement: https://t.co/erd141V5yk https://t.co/H4nXIAGhPr
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