📬 GI Cancer Intelligence Digest — Week 2026-W29

COMPETE and PERISCOPE II Lancet publications, TOPAZ-1 4-year BTC data, and HRS-4642 KRAS G12D PDAC results anchor a GI week dominated by ESMO GI 2026 and daraxonrasib's EMA review.

⚡ TL;DR

📄 Publications

[177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial. — Median PFS 23.9 vs 14.1 months, HR 0.67, p=0.022
Systemic therapy, gastrectomy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy versus systemic therapy alone for gastric cancer with limited peritoneal metastases (PERISCOPE II): final results of a multicentre, randomised, controlled, phase 3 trial after an unplanned commissioned interim analysis. — Median OS 16.6 vs 15.7 months, HR 1.10, p=0.70
KRAS-G12D inhibitor HRS-4642 plus chemotherapy in advanced KRASG12D-mutant pancreatic cancer: a phase 1b/2 trial. — Confirmed ORR 63.3% in 30 treatment-naive patients
Durvalumab Plus Chemotherapy for Advanced Biliary Tract Cancer: A Post Hoc Analysis of the TOPAZ-1 Randomized Clinical Trial. — Median OS 13.0 vs 11.4 months, HR 0.75

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TOURMALINE: real-world durvalumab across seven gemcitabine-based regimens in advanced BTC — TOURMALINE with durvalumab plus 7 gemcitabine-based chemos: ORR 33.1%, mPFS 7.4 mo, mOS 13.5 mo
Update: TOPAZ-1 4-year data reports long-term OS landmark in biliary tract cancer — mOS 13.0 vs 11.4 months (HR 0.75), 48-month OS rate 11.8% vs 4.3%
Spatial multi-omics maps colorectal micrometastasis biology — Study deconstructs clonal evolution of micrometastases and TME differences between micro- and macrometastases in CRC
HRS-4642: intravenous KRAS G12D inhibitor posts high response rate in first-line PDAC — HRS-4642 plus chemo in 30 first-line metastatic PDAC: DCR 93%, median PFS 13.1 months, 12-month OS 83%
Update: daraxonrasib enters EMA CHMP phased review for pretreated metastatic PDAC — The EMA's CHMP has initiated a phased review of daraxonrasib for previously treated metastatic pancreatic cancer

Full details below ↓

📄 What's Being Published

Manuscripts:

[177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial. — Walter Thomas et al., Lancet

In this phase 3 trial, median progression-free survival was significantly longer with [177Lu]Lu-edotreotide versus everolimus (23.9 months [95% CI 18.7–30.0] vs 14.1 months [9.2–20.9]; stratified HR 0.67 [95% CI 0.48–0.95]; p=0.022). Grade 3–4 treatment-related adverse events occurred in 18% of patients in the [177Lu]Lu-edotreotide group versus 40% in the everolimus group.

Clinical bottom line: The full COMPETE publication in the Lancet confirms [177Lu]Lu-edotreotide significantly prolongs PFS over everolimus with a better toxicity profile, supporting its early use in advanced progressive GEP-NETs.

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Systemic therapy, gastrectomy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy versus systemic therapy alone for gastric cancer with limited peritoneal metastases (PERISCOPE II): final results of a multicentre, randomised, controlled, phase 3 trial after an unplanned commissioned interim analysis. — Quik Judith S E et al., Lancet Oncol

Median overall survival in the standard group was 16.6 months (95% CI 14.1–21.9) compared with 15.7 months (95% CI 11.4–25.5) in the experimental group (HR 1.10 [95% CI 0.69–1.74]; p=0.70). Grade 3 or worse adverse events occurred in 21 (42%) of 50 patients in the experimental group versus 10 (20%) of 51 patients in the standard group, with three treatment-related deaths in the experimental arm.

Clinical bottom line: Gastrectomy with cytoreductive surgery and HIPEC provided no survival benefit over systemic therapy alone in gastric cancer with limited peritoneal metastases, and added substantial toxicity.

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KRAS-G12D inhibitor HRS-4642 plus chemotherapy in advanced KRASG12D-mutant pancreatic cancer: a phase 1b/2 trial. — Cui Jiujie et al., Nat Med

The confirmed objective response rate in 30 treatment-naive patients was 63.3% (95% CI 43.9–80.1). Grade ≥3 treatment-related adverse events occurred in 90.3% of patients, primarily hematologic toxicities consistent with AG chemotherapy.

Clinical bottom line: The intravenous liposomal KRAS-G12D inhibitor HRS-4642 with nab-paclitaxel/gemcitabine produced a 63.3% confirmed response rate in first-line KRAS G12D PDAC with a manageable safety profile.

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Mismatch repair deficiency or microsatellite instability in locally advanced rectal cancer patients treated with total neoadjuvant therapy. — Benhima Nada et al., Eur J Cancer

Of 1320 patients (69.1%) with known MMR/MS status, 46 (3.5%) had dMMR/MSI-H tumors. In the matched population, pathologic complete response was 14.2% among pMMR/MSS tumors versus 12.5% among dMMR/MSI-H tumors (adjusted OR 1.07, 95% CI 0.39–2.91, p=0.899).

Clinical bottom line: In locally advanced rectal cancer treated with total neoadjuvant therapy, dMMR/MSI-H status did not hold prognostic value for response or survival.

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Spatial multi-omics landscape of colorectal cancer macro- and micrometastases. — Liu Yang et al., Cancer Cell

The study mapped 49 tumors from 19 patients, encompassing paired primary CRC and matched liver and lung metastases. A CLiMi-specific six-gene signature was identified, associated with MRD status, disease-free survival, and chemotherapy resistance across multiple independent cohorts.

Clinical bottom line: Spatial multi-omics of colorectal metastases reveals a dormant stem-like state in liver micrometastases and a six-gene signature tied to minimal residual disease and chemotherapy resistance.

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Durvalumab Plus Chemotherapy for Advanced Biliary Tract Cancer: A Post Hoc Analysis of the TOPAZ-1 Randomized Clinical Trial. — Oh Do-Youn et al., JAMA Oncol

Median OS was 13.0 months (95% CI 11.6–14.1) with durvalumab plus GemCis versus 11.4 months (95% CI 10.1–12.5) with placebo plus GemCis (HR 0.75; 95% CI 0.64–0.88). The 48-month OS rate was 11.8% versus 4.3%, respectively.

Clinical bottom line: New 4-year TOPAZ-1 follow-up shows durvalumab plus GemCis sustains a long-term survival benefit in advanced biliary tract cancer, with a 48-month OS rate of 11.8% vs 4.3%.

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Real-World Implementation of Tarlatamab-Dlle Therapy for Patients With Extensive-Stage Small Cell Lung Cancer and Other High-Grade Neuroendocrine Neoplasms. — Carlisle Jennifer W et al., JCO Oncol Pract

From June 2024 to September 2025, 49 patients with SCLC were treated on the outpatient protocol. The estimated median PFS was 3.7 months (95% CI 2.7–5.2) and the median OS was 7.1 months (95% CI 4.9–9.3).

Clinical bottom line: Outpatient administration of tarlatamab is safe and feasible with appropriate monitoring for cytokine release syndrome and neurotoxicity.

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Long-Term Outcomes and Surgical Conversion After Immunotherapy in Microsatellite Instability-H Biliary Tract Cancers. — Shah Priyanshi et al., JCO Precis Oncol

Six patients (23.1%) were restaged to resectable from advanced disease after ICI therapy and underwent resection, all remaining recurrence-free at last follow-up; of these, 3 (50%) achieved a pathologic complete response. The median time to treatment discontinuation was 9.9 months (95% CI 5.7–14.5 months) and the 2-year OS was 73% (95% CI 56%–94%).

Clinical bottom line: Immune checkpoint inhibitors in MSI-H biliary tract cancer produced durable responses and downstaged some tumors to resectable disease, supporting up-front dMMR/MSI-H testing.

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🗣️ 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).

TOURMALINE: real-world durvalumab across seven gemcitabine-based regimens in advanced BTC

The TOURMALINE dataset examined durvalumab combined with seven gemcitabine-based chemotherapy regimens, reporting an ORR of 33.1%, median PFS of 7.4 months, and median OS of 13.5 months, with consistent efficacy and safety observed across all seven chemotherapy combinations. Whether these results support flexible chemotherapy backbone selection when pairing durvalumab in first-line biliary tract cancer is an open question for clinicians operating outside trial conditions.

Discussed by: @ArndtVogel, @DraMartinezLago

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Update: TOPAZ-1 4-year data reports long-term OS landmark in biliary tract cancer

The 4-year post hoc analysis of TOPAZ-1 reported a median OS of 13.0 versus 11.4 months (HR 0.75) and a 48-month OS rate of 11.8% versus 4.3% for durvalumab plus GemCis compared to placebo plus GemCis, with safety described as consistent with no new signals. Reporting 4-year OS data in biliary tract cancer is notable for the field, and the identity of the small subset sustaining long-term benefit remains a central question.

Discussed by: @ArndtVogel, @OncoAlert

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Spatial multi-omics maps colorectal micrometastasis biology

Published in Cancer Cell, this spatial multi-omics study of colorectal cancer macro- and micrometastases deconstructs the clonal evolution of micrometastases and tumor microenvironment differences between micro- and macrometastases across 49 tumors from 19 patients. The identification of a CLiMi-specific six-gene signature associated with MRD status, disease-free survival, and chemotherapy resistance raises the question of whether this signature can refine MRD surveillance and chemotherapy decisions in CRC.

Discussed by: @Aiims1742, @OncoAlert

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HRS-4642: intravenous KRAS G12D inhibitor posts high response rate in first-line PDAC

In this phase 1b/2 trial of HRS-4642 plus chemotherapy in 30 first-line metastatic pancreatic cancer patients, the disease control rate was 93%, median PFS was 13.1 months, and OS at 12 months was 83%, with TRAEs described as chemotherapy-related. HRS-4642 plus chemotherapy shows clinical activity in advanced KRAS G12D-mutant pancreatic cancer, and the intravenous liposomal formulation is being assessed for whether it can sidestep the GI toxicity constraints of oral KRAS G12D inhibitors.

Discussed by: @Aiims1742, @PanClawd

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Update: daraxonrasib enters EMA CHMP phased review for pretreated metastatic PDAC

The EMA's CHMP has initiated a phased review of daraxonrasib as a potential treatment for previously treated metastatic pancreatic cancer, while RevMed reportedly nears completion of its rolling NDA submission to the FDA. Whether an accelerated EMA pathway will shift the speed at which pan-RAS inhibitors become available to European PDAC patients is an active point of debate among oncologists.

Discussed by: @CancerNetwrk, @DrMarkLythgoe

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PERISCOPE II: CRS/HIPEC adds no survival benefit in gastric cancer with limited peritoneal metastases

PERISCOPE II compared gastrectomy plus cytoreductive surgery and HIPEC versus systemic therapy alone in gastric cancer with limited peritoneal metastases, finding no OS benefit (15.7 vs 16.6 months, HR 1.10), with grade ≥3 adverse events in 42% of the experimental group versus 20% in the standard group, and three treatment-related deaths versus none. Whether CRS/HIPEC should continue to be offered outside clinical trials for this patient population is now a direct question for surgical and medical oncology teams.

Discussed by: @OncoAlert, @TheLancetOncol

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IMbrave251: PD-L1 blockade beyond progression fails to reach significance in HCC

IMbrave251 reported a median OS of 14.6 versus 12.5 months (HR 0.88; P=0.2115) for atezolizumab continuation beyond progression, with no progression-free survival benefit and only a minimal difference in response rate. Routine continuation of atezolizumab beyond progression is not supported by these data, and physician's choice TKI alone remains the standard second-line approach; whether any HCC subgroup derives meaningful benefit from continued PD-L1 blockade past progression remains unresolved.

Discussed by: @ChandrakanthMv, @mlieducation.bsky.social

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COMPETE published in the Lancet: PRRT beats everolimus in advanced GEP-NETs

The COMPETE trial, now published in the Lancet, showed PFS extended to 23.9 versus 14.1 months (HR 0.67), an ORR of 22% versus 4% with everolimus, and grade 3/4 treatment-related adverse effects dropping from 40% to 18% with [177Lu]Lu-edotreotide. Whether this magnitude of PFS benefit and the more favorable toxicity profile are sufficient to move PRRT earlier in the GEP-NET treatment sequence, ahead of everolimus, is now a concrete sequencing question for specialists.

Discussed by: @CancerNetwrk, @OncUpdates

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🔥 Top Ranked Tweets

Vivek Subbiah, MD @VivekSubbiah

Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial | Nature Medicine https://t.co/D0WeiYbKOv

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