📬 GI Cancer Intelligence Digest — Week 2026-W44

MASTERPLAN in Lancet Oncology: adding SBRT to perioperative chemotherapy cuts locoregional recurrence in high-risk localized pancreatic cancer

Adding SBRT to perioperative chemotherapy more than halved locoregional recurrence, and clinicians also highlighted gains in PFS and overall survival in this small phase 2 trial. Critics pointed out that only 40/49 patients assigned to SBRT received it under an intention-to-treat analysis. They also flagged a mixed population (59% borderline resectable), early OS curve separation and a poor control-arm median OS with n=25. With adjuvant chemotherapy given to 80% vs 36% of resected patients, the debate is whether the survival signal belongs to SBRT itself or whether the trial should change practice only on local control.

Key numbers: 12-mo locoregional recurrence 20·2% vs 52·0%, sHR 0·44 · PFS 11.9 vs 6.3 mo, HR 0.44 · OS 22.0 vs 14.0 mo, HR 0.45 · Grade ≥3 SAEs 64% vs 56%

Discussed by: @_ShankarSiva, @jryckman3, @NiuSanford, @GIMedOnc, @graokane, @TapiaJC1, @JoeChangMD

→ View representative tweet

Sources cited: Perioperative chemotherapy and stereotactic body radiotherapy versus perioperative chemot… (Lancet Oncol) · Elsevier

NICHE-2 five-year data in The Lancet: 100% disease-free and overall survival after four weeks of neoadjuvant ipilimumab/nivolumab in dMMR colon cancer

Patients with locally advanced dMMR colon cancer received one dose of ipilimumab and two of nivolumab, then surgery, and there were zero events: "a flat line." Nearly all patients cleared ctDNA before surgery, all were ctDNA negative afterward, and no new safety signals emerged. Because the trial is single-arm and overall survival was an exploratory post-hoc analysis, clinicians argue a randomized comparison is still owed before this replaces surgery-first. Others ask whether the next trial should instead test omitting surgery altogether.

Key numbers: 3-y DFS 100% vs prespecified 93% (p<0.0001) · 5-year OS 100% · ctDNA clearance 82% pre-op · Grade 3–4 TRAE 4%

Discussed by: @dr_yakupergun, @GIMedOnc, @ArndtVogel, @DraMartinezLago, @DrAllanPereira, @YGaritaonaindia, @jryckman3, @CathyEngMD

→ View representative tweet

Sources cited: Elsevier · Disease-free survival and overall survival after neoadjuvant immunotherapy in mismatch re… (Lancet) · Elsevier

RASolute 302 subgroup analyses at ESMO: daraxonrasib overall survival benefit holds across RAS genotypes in previously treated metastatic pancreatic cancer

The RAS(ON) inhibitor daraxonrasib roughly halved the risk of death versus chemotherapy in previously treated metastatic pancreatic cancer, and the benefit held across G12D, G12V, Q61 and RAS wild-type subgroups. G12R showed a wide confidence interval, and FDA NDA review data leave open whether RAS inhibition is as effective for KRAS wild-type and whether 300 mg is necessary. With 8.5 months of median follow-up and underpowered subgroups, clinicians debate whether G12R and RAS wild-type patients should be counselled differently.

Key numbers: OS 13.2 vs 6.7 mo, HR 0.40 · PFS 7.2 vs 3.6 mo, HR 0.49 · ORR 32% vs 11%

Discussed by: @DraMartinezLago, @DrDanielKing, @graokane, @TapiaJC1, @ArndtVogel, @DrAngelaLamarca, @SuyogCancer

→ View representative tweet

FDA accelerated approval of dostarlimab for stage II/III dMMR/MSI-H locally advanced rectal cancer on AZUR-1

The FDA granted accelerated approval to dostarlimab, dosed at 500 mg IV every 3 weeks for 9 cycles, for stage II or III dMMR or MSI-H locally advanced rectal cancer. The approval is based on AZUR-1, in which most patients received dostarlimab alone with no further treatment and no progression. Clinicians note the approval rests on a single-arm phase 2, so survival equivalence will depend on real-world data. The sustained clinical complete response rate differed between investigator and central review, which used different evaluable populations, and that raises the question of how to judge residual disease before committing a patient to surveillance.

Key numbers: 12-mo sustained cCR 47% central vs 68% investigator · ORR 79% · cCR12 + pCR 76% · 98% durable cCR

Discussed by: @OncBrothers, @OncoAlert, @GIMedOnc, @NiuSanford, @ozdogan_md, @MarioBalsaMD, @dr_yakupergun, @jryckman3, @EvelynWongYT

→ View representative tweet

Sources cited: FDA press release · OncLive

AMPLIFY-7P in Nature Medicine: the mKRAS amphiphile vaccine misses its DFS endpoint but ctDNA emerges as the dominant prognostic driver

Camupepimut did not significantly improve DFS in resected KRAS-mutated pancreatic cancer, even though nearly every vaccinated patient mounted mKRAS-specific T cells and the strongest responders had the lowest recurrence rates. Clinicians called the post hoc ctDNA panel the most important finding: in the post-surgical setting, ctDNA positivity is the pivotal driver of disease-free survival, agnostic to vaccine. Some noted that immunogenicity may be uncoupled from clinical benefit. The open question is whether the confirmatory phase 3 should enrol only ctDNA-negative patients.

Key numbers: Median DFS 23.8 vs 21.2 mo, HR 0.85 · ctDNA+ adjusted HR 5.99 · T cell responders DFS not reached vs 6.08 mo, HR 0.22 · 6-mo DFS 75.7% vs 61.7%, HR 0.55

Discussed by: @LorenzaRimassa, @Aiims1742, @graokane, @ArndtVogel, @DrAngelaLamarca, @KlebanoffLab

→ View representative tweet

Sources cited: Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic cancer: the randomiz… (Nat Med) · OncoDaily

PRABITAS published in The Lancet: biweekly FTD/TPI plus bevacizumab is non-inferior to the conventional schedule with a third of the grade 3+ neutropenia

The 14-day FTD/TPI plus bevacizumab schedule was non-inferior on overall survival, with identical PFS, and it sharply reduced neutropenia, G-CSF use and anorexia. US clinicians say the trial prospectively validates a real-world dosing approach already in use. Two treatment-related deaths in the 14-day arm and a Japan-only population frame the debate over whether to adopt the schedule immediately as default or wait for guidelines.

Key numbers: mOS 11.3 vs 10.3 mo, HR 0.93 · PFS 3.9 vs 3.9 mo · G≥3 neutropenia 13% vs 39% · G-CSF use 3% vs 13% · FN 1% vs 5%

Discussed by: @DraMartinezLago, @ArndtVogel, @CathyEngMD, @UGrewalMD, @DaisukeKotani

→ View representative tweet

Encorafenib/cetuximab beyond progression: ECLYPse meets its endpoint while TRIDENTE and BRICKET rechallenge data split

ECLYPse, which continued encorafenib plus cetuximab beyond progression with FOLFIRI, met its primary endpoint, although OS is still immature. In the rechallenge trials, TRIDENTE (encorafenib, binimetinib and cetuximab) was read as positive, while GONO BRICKET (N=16) missed its primary endpoint with no responses. Discussants noted that PFS was almost identical across TRIDENTE and BRICKET, and attributed the differing ORR to prior-responder selection and the added binimetinib. Clinicians argue that on progression on first-line mFOLFOX plus encorafenib/cetuximab, the EGFR/BRAF backbone should be kept and paired with mFOLFIRI rather than dropped and later rechallenged.

Key numbers: ECLYPse 6-mo PFS 69.5% · TRIDENTE ORR 19% · TRIDENTE vs BRICKET mPFS 2.8 vs 2.9 mo

Discussed by: @CathyEngMD, @ArndtVogel, @UGrewalMD, @DraMartinezLago, @GlopesMd

→ View representative tweet

UK consensus extends Lynch syndrome testing beyond colorectal and endometrial cancer

The consensus recommends upfront germline testing for dMMR/MSI tumours of the urinary tract, small bowel, pancreas, adrenal, sebaceous glands and glioma, with MLH1 methylation triage for gastric tumours. Clinicians position MSI/MMR testing as guiding immunotherapy as well as flagging Lynch syndrome, though making timely testing accessible across healthcare systems remains a challenge. A meta-analysis found pathogenic or likely pathogenic variants in 15.2% of patients with colorectal cancer, including 13% diagnosed at age 50+. Against that background, the debate is whether reflex germline testing should apply to every dMMR tumour or be focused on the patients most likely to carry a variant.

Discussed by: @DraMartinezLago, @sciqst, @AGA_GIHN

→ View representative tweet

Sources cited: UK consensus recommendations for onward testing for Lynch syndrome in patients with defic… (Journal of Medical Genetics, 2026) · FDA press release · FDA press release

ACTICCA-1: adjuvant cisplatin/gemcitabine does not beat capecitabine after curative resection of biliary tract cancer

Adjuvant CisGem numerically lengthened disease-free survival over capecitabine but missed statistical significance on log rank. It did not significantly improve overall survival and carried the expected doublet toxicity. No major subgroup difference was seen for intrahepatic disease, and clinicians conclude that success in metastatic disease did not translate to the adjuvant setting, leaving capecitabine as standard. Discussion now centres on whether any subgroup, such as node-positive or intrahepatic disease, justifies the doublet.

Key numbers: mDFS 25.7 vs 17.9 mo (p=0.097) · RMST DFS +2.6 mo (p=0.011) · mOS 58.1 vs 48.2 mo · DFS at 2 yrs 52 vs 44%

Discussed by: @ArndtVogel, @graokane, @DaniCastilloMD, @DrAngelaLamarca, @DraMartinezLago, @lucykflanders

→ View representative tweet

LOMAC: four months of adjuvant XELOX is non-inferior to six months after D2 gastrectomy

Four months of adjuvant XELOX was non-inferior to six months for 3-year DFS after D2 resection of stage II–III gastric cancer, with fewer severe adverse events and higher completion. Radiation oncologists called the de-escalation important because tolerance of these regimens is a major issue. The debate is whether four months should become the default or whether the Chinese-only population limits generalisability.

Key numbers: 3-y DFS 69.2% vs 70.8%, HR 1.01 · G≥3 AEs 8.4% vs 15% · Completion 83.6% vs 60.4%

Discussed by: @DraMartinezLago, @_ShankarSiva, @Erman_Akkus

→ View representative tweet

SANO five-year results in Annals of Oncology: active surveillance matches surgery on survival but with 17 more distant metastases per 100 patients

Five-year overall survival and disease-free survival did not differ significantly between active surveillance and surgery. However, distant metastases and oesophageal cancer deaths were more frequent with surveillance. Radiation oncologists stress that the regimen used only 41.4 Gy/23 fx, a pre-operative and arguably non-definitive dose, with ~75% adenocarcinoma. Clinicians call SANO neither positive nor negative, and ask whether the metastatic excess is an acceptable trade for organ preservation and whether the trial still applies now that FLOT is used in place of CROSS.

Key numbers: 5-y OS 50% vs 54%, HR 1.17 · Distant metastases 46% vs 29% · Esophageal cancer death 40% vs 30%, HR 1.67 · DFS HR 1.39

Discussed by: @GIMedOnc, @jryckman3, @NiuSanford, @ozdogan_md, @SuyogCancer, @DraMartinezLago, @ArndtVogel, @ChandrakanthMv

→ View representative tweet

Sources cited: Elsevier

HARMONi-GI1 presidential data: ivonescimab plus gem/cis beats durvalumab plus gem/cis head-to-head in first-line advanced biliary tract cancer

The PD-1/VEGF bispecific ivonescimab plus gemcitabine/cisplatin showed OS superiority over durvalumab plus gemcitabine/cisplatin, with PFS and ORR also positive and no new safety signals. Commentators stress that the comparator was an active standard rather than placebo. Because the trial was conducted in China, they also want data on magnitude, toxicity and generalisability, and question whether a Western trial is needed before practice changes.

Key numbers: Median OS 14.9 vs 12.1 mo, HR 0.75 · Median PFS 8.4 vs 5.8 mo, HR 0.61 · ORR 53.8% vs 32.5%

Discussed by: @SuyogCancer, @LorenzaRimassa, @ArndtVogel, @ozdogan_md, @ChandrakanthMv

→ View representative tweet

Two CLDN18.2 ADCs read out at the ESMO presidential: G-HOPE-001 arcotatug tavatecan and CLARITY-Gastric 01 sonesitatug vedotin

Arcotatug tavatecan, a TOPO-I payload ADC tested in CLDN18.2 high-expressing gastric/GEJ cancer after multiple lines, improved PFS, interim OS and response, and no interstitial lung disease was observed. Sonesitatug vedotin improved overall survival, including in patients with lower CLDN18.2 expression, but PFS did not meet significance. Clinicians argue that CLDN18.2 IHC stops being a one-time first-line question, and they debate whether payload matters more than expression level and whether benefit persists after zolbetuximab.

Key numbers: G-HOPE-001 PFS 5.5 vs 2.9 mo, HR 0.47 · G-HOPE-001 OS 9.9 vs 7.4 mo, HR 0.63 · G-HOPE-001 ORR 23.6% vs 5.3% · CLARITY 3L+ OS 10.0 vs 5.0 mo, HR 0.47 · CLARITY PFS 4.2 vs 3.8 mo, HR 0.77

Discussed by: @SuyogCancer, @GIMedOnc, @ArndtVogel, @ChandrakanthMv, @DaniCastilloMD, @DrVilmaPBarcia, @PTarantinoMD

→ View representative tweet

BGB-B2033, a GPC3 x 4-1BB bispecific, shows activity in heavily pretreated advanced hepatocellular carcinoma

BGB-B2033 conditionally activates 4-1BB on GPC3-expressing tumour cells, aiming for targeted T-cell activity with limited off-tumour toxicity. It showed activity across doses in patients of whom two thirds had more than 2 prior lines, with favourable toxicity, and 450 mg was selected as the recommended phase 2 dose ahead of the phase 3 GroundBBreaker 301. The remaining questions are durability of response and whether pairing with PD-1 blockade such as tislelizumab should be established before phase 3.

Discussed by: @graokane, @ArndtVogel, @hongjaechon, @DrAngelaLamarca, @ronanhsieh

→ View representative tweet

GFH276 pan-RAS molecular glue phase 1/1b in pancreatic cancer raises the sequencing question for RAS inhibitors

In 73 PDAC patients with a median of 2 prior lines, the pan-RAS(ON) molecular glue GFH276 produced an ORR of 41% at 40-160 mg, with rash the most common adverse event. In related chemotherapy-free combinations, daraxonrasib plus vopimetostat reached an 81.8% confirmed ORR (18/22), although commentators note that cohort was predominantly G12V/G12R, which complicates attribution. As RAS-directed trials move quickly to first line, clinicians ask how to sequence a pan-RAS agent against an allele-selective one.

Discussed by: @graokane, @UGrewalMD, @DavidHongMD

→ View representative tweet

KEYNOTE-975: pembrolizumab added to definitive chemoradiotherapy fails in unresectable oesophageal/GEJ cancer even at PD-L1 CPS ≥10

Adding pembrolizumab to definitive chemoradiotherapy did not improve EFS or OS even at PD-L1 CPS ≥10, and it added fatal toxicity and discontinuations. The statistical hierarchy stopped after EFS, so OS was not formally tested. Radiation dose was also not randomized, with sites choosing between FP + 50 Gy, FP + 60 Gy and FOLFOX + 50 Gy. Commentators call it a clean negative at a cost and debate why checkpoint blockade helps after chemoradiotherapy in PACIFIC and CheckMate 577 but not concurrently, pointing to timing, lymphopenia or patient selection.

Key numbers: EFS 15.2 vs 14.7 mo, HR 0.97 · OS 32.2 vs 35.0 mo, HR 1.00 · Grade 5 AEs 13% vs 10% · Discontinuation 34% vs 27%

Discussed by: @ChandrakanthMv, @jryckman3, @ozdogan_md, @nataliagandur, @DraMartinezLago, @ArndtVogel, @weoncologists

→ View representative tweet

HERIZON-GEA-01 second interim OS: the zanidatamab doublet now wins over trastuzumab, and the tislelizumab triplet misses significance by a hair

At the second interim analysis, zanidatamab plus chemotherapy now has its own overall survival win over trastuzumab, and adding tislelizumab extended median OS further. However, the triplet's advantage over the doublet was statistically borderline. Critics note that the control arm received no pembrolizumab, which most PD-L1 CPS ≥1 US patients would get, and that the triplet's gain in the TAP ≥1 subgroup was exploratory and not significant. Considering toxicity, clinicians ask which patients actually need tislelizumab added.

Key numbers: Median OS 27.0 vs 22.9 vs 19.6 mo · 3-year OS 39.8% vs 31.5% vs 22.9% · Doublet vs trastuzumab HR 0.76 · Triplet vs doublet HR 0.81, p=0.0502

Discussed by: @GIMedOnc, @dr_yakupergun, @DrVilmaPBarcia, @OncBrothers, @ArndtVogel, @Dr_Oncologista

→ View representative tweet

COMPANION-002 in JCO: tovecimig plus paclitaxel improves response and PFS in second-line biliary tract cancer but not overall survival

Tovecimig plus paclitaxel improved response and more than halved progression risk, but showed no overall survival difference. Clinicians say crossover makes the OS analysis uninterpretable. Toxicity was substantial, including frequent severe hypertension and discontinuations, and the debate is whether this justifies second-line use or whether development should move to first line.

Key numbers: ORR 18.0% vs 5.3% · PFS 4.7 vs 2.6 mo, HR 0.44 · OS HR 1.05 · Grade ≥3 TEAEs 93.5% vs 64.2% · Discontinuation 40% vs 15%

Discussed by: @graokane, @ArndtVogel, @ilyassahinMD, @UGrewalMD, @nataliagandur, @DraMartinezLago

→ View representative tweet

Sources cited: ASCO Publications

Real-world prognostic model in biliary tract cancer: no benefit continuing chemotherapy beyond 6 months, and CisGem outperforms GEMOX

Real-world data from patients treated with chemotherapy for biliary tract cancer showed no benefit to continuing chemotherapy beyond 6 months. CisGem outperformed GEMOX, and in ECOG 2 patients CisGem gave better OS than gemcitabine alone. Clinicians called these important real-world questions, and the debate is whether to stop at 6 months by default and abandon GEMOX even in ECOG 2 patients.

Discussed by: @ronanhsieh, @ArndtVogel

→ View representative tweet

Sources cited: Elsevier · JAMA Network

Temab-A plus bevacizumab published in Annals of Oncology: c-Met ADC outperforms FTD/TPI plus bevacizumab in refractory colorectal cancer

The c-Met ADC Temab-A with bevacizumab produced responses where FTD-TPI plus bevacizumab produced none, along with longer PFS and OS, although the OS confidence interval crossed 1. Haematological toxicity, including frequent severe neutropenia, matters to clinicians. Lisa Salvatore asked what bevacizumab adds, whether c-Met can guide selection and what the optimal dose is, pending phase 3 validation.

Key numbers: mOS 14.7 vs 10.2 mo, HR 0.62 · ORR 30% vs 0% · Median PFS 6.8 vs 4.2 mo

Discussed by: @ArndtVogel, @CathyEngMD, @DraMartinezLago, @EvelynWongYT

→ View representative tweet

DEWI phase II: dostarlimab with watch-and-wait achieves organ preservation in localized dMMR/MSI-H gastroesophageal adenocarcinoma

Dostarlimab produced a 1-year clinical complete response rate of 62.5% (15/24) at the first interim analysis. Later reporting showed 67.4% (29/43) achieving cCR with organ preservation and no relapse or death among watch-and-wait patients, at 14.9 months of follow-up. Grade 3–4 dostarlimab-related AEs occurred in 21%, and all patients who went to surgery achieved R0 resection. Clinicians frame this as the next frontier after rectal cancer despite interim, small-n data, and ask how a complete response can be confirmed without gastrectomy before offering watch-and-wait outside a trial.

Discussed by: @dr_yakupergun, @GIMedOnc, @DrVilmaPBarcia, @jryckman3, @nataliagandur, @DraMartinezLago

→ View representative tweet

KC-WISE updated OS: anbenitamab plus chemotherapy doubles survival in HER2-positive gastric cancer after trastuzumab

Anbenitamab plus chemotherapy doubled overall survival over chemotherapy after trastuzumab in HER2-positive gastric/GEJ cancer, with large gains in PFS and response and no unexpected safety signal. Clinicians note the bar was not high because the control was single-agent chemotherapy, but the result supports sequential HER2 targeting. The open question is whether a second biparatopic HER2 antibody still works in second line once zanidatamab moves to first line, or whether that slot belongs to trastuzumab deruxtecan.

Key numbers: OS 19.6 vs 9.6 mo, HR 0.39 · PFS 7.1 vs 2.7 mo · ORR 56% vs 14% · G≥3 TEAEs 74.2% vs 54.5%

Discussed by: @GIMedOnc, @DraMartinezLago, @ArndtVogel

→ View representative tweet

RAMIRIS final results: FOLFIRI plus ramucirumab misses co-primary endpoints but improves PFS in taxane-pretreated gastroesophageal adenocarcinoma

FOLFIRI plus ramucirumab missed its co-primary OS and response endpoints against paclitaxel plus ramucirumab but significantly lengthened PFS. Clinicians say paclitaxel-ramucirumab remains standard, and some argue the trial should have been designed for non-inferiority. FOLFIRI-ramucirumab is seen as a reasonable option for patients with limiting neuropathy, and the debate is whether to reserve it for that group only.

Key numbers: OS 8.7 vs 7.5 mo, HR 0.95 · ORR 25.3% vs 22.6% · PFS 5.5 vs 3.7 mo, HR 0.70 · G≥3 AEs 70% vs 68%

Discussed by: @DraMartinezLago, @ArndtVogel, @nataliagandur, @RyanAugustinMD

→ View representative tweet