📬 GI Cancer Intelligence Digest — Week 2026-W43
ESMO's new gastric/oesophageal guideline and NCCN pancreatic v4.2026 landed alongside daraxonrasib's positive CHMP opinion, 4-year NEONIPIGA follow-up, KEYNOTE-966 3-year data, and positive phase 3 ACTION-1 results for 225Ac-DOTATATE in GEP-NETs.
⚡ TL;DR
📄 Publications
- Pancreatic Adenocarcinoma, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology. — The guideline provides diagnostic workup, staging and treatment recommendations across resectable, borderline resectable, unresectable, locally advanced and metastatic disease
- Nivolumab-Ipilimumab for Localized Microsatellite Instability-High Gastric/Gastroesophageal Junction Adenocarcinoma: The Phase 2 NEONIPIGA Nonrandomized Clinical Trial. — French multicenter single-arm phase 2 of neoadjuvant nivolumab 240 mg every 2 weeks for 6 cycles plus ipilimumab 1 mg/kg every 6 weeks for 2 cycles, surgery, then adjuvant nivolumab 480 mg every 4 weeks for 9 cycles, in 32 patients (16 gastric, 16 GEJ)
🐦 Twitter / 🦋 Bluesky
- New ESMO Clinical Practice Guideline for gastric and oesophageal cancer puts four biomarkers at the centre of first-line choice — and recommends a regimen the EMA has not approved — The guideline covers the full patient journey from diagnosis and staging through treatment and follow-up, with recommendations tailored by stage, prior therapy and molecular profile
- Update: checkpoint-inhibitor-based downstaging before liver transplant for HCC beyond Milan now in JAMA Oncology, with the rejection signal front and centre — ICI versus non-ICI downstaging gave ORR 48.1% vs 19.2% and downstaging to Milan in 15.4% vs 8.7%
- Update: FDA approval of adjuvant atezolizumab for stage III dMMR colon cancer gets a pathology and label-breadth critique, and a NICHE-2 comparison — ATOMIC randomized 712 patients to 6 months of mFOLFOX6 with atezolizumab then 6 months of atezolizumab alone versus 6 months of mFOLFOX6 alone, with 3-year DFS 86.3% vs 76.2%, HR 0.50 (95% CI 0.35-0.73)
- Real-world comparison of atezolizumab/bevacizumab versus durvalumab/tremelimumab in unresectable HCC with portal vein tumour thrombus — 1,201 Child-Pugh A patients were compared, ATZ/BEV (n=1,015) versus DUR/TRE (n=186), with ORR 31.0% vs 31.7% (p=0.86) and DCR 78.4% vs 62.4% (p<0.01)
- Total neoadjuvant therapy in locally advanced rectal cancer: JCO analysis separates low- from mid-rectal tumours — The JCO analysis draws clinical and therapeutic distinctions between low- and mid-rectal cancers in total neoadjuvant therapy for locally advanced rectal cancer
Full details below ↓
📄 What's Being Published
NCCN Guidelines® Insights: Hepatocellular Carcinoma, Version 2.2026. — Benson Al B et al., J Natl Compr Canc Netw
The NCCN HCC Guidelines provide recommendations for the comprehensive care of patients with HCC, including screening, evaluation, treatment and surveillance. HCC is the most common primary cancer of the liver. The multidisciplinary panel meets at least once a year to update the guidelines based on new and emerging data.
Clinical bottom line: This Insights article summarizes recent NCCN HCC updates. It is a reference document and does not change practice on its own.
Pancreatic Adenocarcinoma, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology. — Ko Andrew H et al., J Natl Compr Canc Netw
The guideline covers diagnostic workup, staging and treatment across resectable, borderline resectable, unresectable, locally advanced and metastatic disease. Tumour NGS is recommended for every patient who is a candidate for anticancer therapy, with RNA sequencing added for fusion detection. Neoadjuvant PAXG is listed as useful in certain circumstances, based on an Italian phase 3 result against mFOLFIRINOX (median EFS 16.0 vs 10.2 months, HR 0.63). The panel declines to make a consensus recommendation on postoperative ctDNA.
Clinical bottom line: Every pancreatic adenocarcinoma patient who is a treatment candidate should now have tumour NGS with RNA sequencing. After neoadjuvant therapy, resection decisions should rest on biological response rather than vascular contact alone.
Treatment of Advanced Biliary Tract Cancer: ASCO Living Guideline, Version 2026.1.0. — Shroff Rachna T et al., J Clin Oncol
Broad-based tissue DNA and RNA NGS is recommended at diagnosis at any stage. Plasma liquid biopsy is generally reserved for cases where tissue is unavailable. First-line therapy for pMMR/MSS disease is an immune checkpoint inhibitor plus chemotherapy, and pembrolizumab monotherapy is an option for dMMR/MSI-H disease. After progression without identified biomarkers, FOLFOX with active symptom control, or active symptom control alone, is recommended. Biomarker-specific second-line options cover dMMR/MSI-H, IDH1, FGFR2, BRAF V600E, HER2, RET, NTRK1/2/3 and NRG1 alterations.
Clinical bottom line: ASCO now formalizes tissue DNA+RNA NGS at diagnosis for every advanced biliary tract cancer and reserves plasma liquid biopsy for when tissue is unavailable. Second-line choices follow a biomarker-defined menu.
Radiotherapy combined with serplulimab, and chemotherapy as first-line treatment for metastatic pancreatic adenocarcinoma: a multicenter, single-arm, phase II trial. — Cheng Ke et al., Clin Cancer Res
Forty-six patients received at least one dose of treatment. The 6-month PFS rate was 78.3% (95% CI, 67.2%-91.1%) against a predefined target of 60%, and the objective response rate was 73.9% (95% CI, 58.9%-85.7%). Median PFS was 8.5 months and median OS 14.0 months, with no treatment-related deaths or unexpected safety signals.
Clinical bottom line: A 73.9% response rate and 78.3% 6-month PFS are striking for a single-arm phase II in metastatic pancreatic cancer. Without a randomized comparator, this regimen belongs in trials, not the clinic.
Cobimetinib + Vemurafenib in Patients With BRAF V600E-Mutant Papillary Thyroid and Biliary Tract Cancers: Results From the TAPUR Study. — Diamond-Rossi Samantha A et al., JCO Precis Oncol
In the biliary tract cancer cohort (N = 18; n = 15 evaluable), disease control and objective response rates were 67% and 53%. In the thyroid cohort, the corresponding rates were 94% and 63%. The null hypothesis of a 15% disease control rate was rejected for both cohorts (P < .0001). Twenty-one patients (53%) had at least one treatment-related grade 3 to 4 or serious adverse event.
Clinical bottom line: A 53% response rate supports BRAF/MEK blockade as a real option in BRAF V600E biliary tract cancer, despite 53% grade 3-4 toxicity.
Nivolumab-Ipilimumab for Localized Microsatellite Instability-High Gastric/Gastroesophageal Junction Adenocarcinoma: The Phase 2 NEONIPIGA Nonrandomized Clinical Trial. — Samaille Thomas et al., JAMA Oncol
The trial enrolled 32 patients (16 gastric, 16 GEJ), with median follow-up of 48.3 months. Four-year OS was 84.1% (95% CI, 65.8%-93.0%), and 4-year EFS was 83.5% in the 31 patients eligible for surgery. Seventeen of 29 patients (59%) achieved pCR, and all non-operated patients achieved a clinical complete response. Neoadjuvant and adjuvant grade 3/4 adverse events occurred in 6 (19%) and 4 patients (17%), respectively.
Clinical bottom line: Survival is durable, but the authors found no clear evidence of improvement over surgery alone. This supports randomized organ-preservation trials, not a new standard of care.
🗂 Every paper considered this week, including the ones that didn’t make it →
🗣️ 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).
New ESMO Clinical Practice Guideline for gastric and oesophageal cancer puts four biomarkers at the centre of first-line choice — and recommends a regimen the EMA has not approved
The guideline makes HER2, MSI, CLDN18.2 and PD-L1 testing central to first-line choice. Checkpoint inhibitor thresholds differ by agent: nivolumab at CPS ≥5, pembrolizumab at CPS ≥1 and tislelizumab at TAP ≥5%. Zolbetuximab is recommended for CLDN18.2+ disease at ≥75% tumour cells IHC 2+/3+. D-FLOT is preferred for resectable adenocarcinoma, and FLOT is favoured over CROSS at the junction, although CROSS remains relevant for patients unsuitable for FLOT. The debate centres on two points: the HER2+ recommendation of zanidatamab + tislelizumab + chemotherapy is FDA-approved but not yet EMA-approved, and CROSS's role at the junction is now uncertain.
Key numbers: MATTERHORN EFS HR 0.71 · MATTERHORN OS HR 0.78 · pCR 19.2% vs 7.2% · ESOPEC mOS 66 vs 37 mo, HR 0.70
Discussed by: @ArndtVogel, @ChandrakanthMv, @dr_yakupergun, @DraMartinezLago, @DrAllanPereira, @ChandrakanthMv
Sources cited: Annals of Oncology
Update: checkpoint-inhibitor-based downstaging before liver transplant for HCC beyond Milan now in JAMA Oncology, with the rejection signal front and centre
In HCC initially beyond Milan, ICI-based multimodal downstaging before transplant was linked to higher response rates, more successful downstaging, and longer OS and RFS than non-ICI downstaging. The cost was a doubling of acute rejection within 90 days. Complete pathologic response tracked with better survival, but imaging-pathology concordance was poor. Clinicians are weighing whether the rejection signal is an acceptable price and how long a washout before transplant is enough.
Key numbers: ORR 48.1% vs 19.2% · Median OS 4.57 vs 2.53 yrs, HR 0.63 · RFS 1.47 vs 0.89 yrs, HR 0.59 · 90-day acute rejection 16.3% vs 8.2% · cPR vs no cPR 5-yr OS 86.6% vs 77.4%
Discussed by: @hongjaechon, @hongjaechon, @ArndtVogel
Sources cited: JAMA Network · ovid.com · Elsevier
Update: FDA approval of adjuvant atezolizumab for stage III dMMR colon cancer gets a pathology and label-breadth critique, and a NICHE-2 comparison
In ATOMIC, atezolizumab with mFOLFOX6 roughly halved the risk of recurrence or death, but OS is not mature. The approval covers adults and paediatric patients ≥2 years, and the label permits "a fluoropyrimidine" with oxaliplatin even though only mFOLFOX6 was tested. Atezolizumab with CAPOX is therefore an extrapolation without randomised evidence. Retrospective central review reclassified some submitted specimens as pMMR or inconclusive, which raises the debate over how much MMR testing quality assurance should be mandatory before committing a patient to a year of immunotherapy.
Key numbers: 3-yr DFS 86.3% vs 76.2%, HR 0.50 · 5-yr OS 89.7% vs 87.9%, HR 0.90 · Grade 3–4 AEs 84.1% vs 71.9% · Treatment-attributed grade 3/4 AEs 72.5% vs 61.7%
Discussed by: @EladSharonMD, @ChandrakanthMv, @GlopesMd, @DraMartinezLago, @EladSharonMD
Sources cited: Atezolizumab plus FOLFOX for Stage III Mismatch Repair–Deficient Colon Cancer (New England Journal of Medicine, 2026) · FDA press release · OncoDaily
Real-world comparison of atezolizumab/bevacizumab versus durvalumab/tremelimumab in unresectable HCC with portal vein tumour thrombus
In this multicenter real-world Child-Pugh A cohort with PVTT, response rates were similar between regimens. Atezolizumab/bevacizumab gave better disease control and PFS, while overall OS did not differ significantly. In the Vp4 subgroup, OS favoured atezolizumab/bevacizumab, but the difference attenuated in an 8-week landmark analysis, so the finding is hypothesis-generating. The open question is whether Vp4 should steer first-line choice or whether the gap reflects early-death immortal-time bias.
Key numbers: ORR 31.0% vs 31.7% · DCR 78.4% vs 62.4% · mPFS 6.9 vs 5.3 mo · mOS 24.9 vs 31.0 mo · Vp4 mOS 16.6 vs 6.1 mo, HR 3.60
Discussed by: @hongjaechon, @ArndtVogel
Sources cited: Atezolizumab plus Bevacizumab Versus Durvalumab plus Tremelimumab in Unresectable Hepatoc… (Liver Cancer, 2026) · Elsevier
Total neoadjuvant therapy in locally advanced rectal cancer: JCO analysis separates low- from mid-rectal tumours
A JCO analysis draws clinical and therapeutic distinctions between low- and mid-rectal cancers treated with total neoadjuvant therapy. Phase 3 UNION reported a 3-year EFS of 91.3% vs 77.4% (HR 0.33, p=0.0029) with short-course radiotherapy followed by camrelizumab + CAPOX versus long-course CRT followed by CAPOX. It is the first phase 3 to show an EFS benefit with a checkpoint inhibitor in rectal cancer. However, the arms differed in both radiotherapy schedule and immunotherapy use, so it is unclear how much of the gain belongs to the checkpoint inhibitor.
Discussed by: @DaisukeKotani, @GIMedOnc
Sources cited: Disruptive Analysis of Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Clini… (Journal of Clinical Oncology, 2026)
Update: the week before ESMO 2026, GI oncologists publish competing lists of which abstracts will change practice
AZUR-1 tests dostarlimab alone in 154 patients with stage II/III MSI-H rectal cancer, and ACTICCA-1 compares adjuvant gemcitabine + cisplatin against capecitabine after resected biliary tract cancer. AMPLIFY-7P, testing the mKRAS vaccine ELI-002 7P after PDAC resection, missed its DFS endpoint. Two phase 3 CLDN18.2 ADC trials were positive: CLARITY-Gastric01 for OS and G-HOPE-001 for PFS. HARMONi-GI1, testing ivonescimab against durvalumab with GemCis, was positive for OS. Clinicians are debating which readout changes Monday practice, noting that these are pre-meeting predictions made before the abstract text was released.
Discussed by: @jgong15, @GIMedOnc, @MarioBalsaMD
KEYNOTE-966 3-year follow-up: pembrolizumab plus gem/cis keeps an OS benefit in advanced biliary tract cancer, but the absolute gain is 2 percentage points
Longer-term follow-up of the double-blind, placebo-controlled phase 3 trial shows a maintained OS benefit with no new safety signals. Survival improves even though response rates are identical between arms. With only a small absolute 3-year survival gain, clinicians question whether pembrolizumab should be added for every pMMR/MSS patient or reserved for those likely to get durable benefit.
Key numbers: Median OS 12.7 vs 10.9 mo, HR 0.86 · 3-yr OS 13% vs 11% · Median PFS 6.5 vs 5.6 mo · Grade 3–4 TRAEs 70% vs 69%
Discussed by: @OncoAlert, @hongjaechon, @DraMartinezLago
Sources cited: Elsevier · ScienceDirect
Phase 3 ACTION-1 positive: 225Ac-DOTATATE (RYZ101) improves PFS in SSTR+ GEP-NETs that progressed after lutetium-177
Bristol Myers Squibb announced that the ACTION-1 interim analysis of RYZ101 significantly improved PFS versus standard-of-care options after progression on 177Lu. These are the first phase 3 data for an alpha-emitting radiopharmaceutical. The hazard ratio, absolute PFS benefit, OS and quality of life have not yet been reported. Open questions include cumulative renal and marrow toxicity, isotope supply, equitable access, and optimal sequencing, which feeds the debate over whether a PFS-only interim readout justifies moving into the post-177Lu slot.
Discussed by: @OncoAlert, @OncoAlert, @UGrewalMD, @OncoAlert
Sources cited: Evaluation of early C‐reactive protein kinetics as an early response marker in biliary tr… (Cancer, 2026)
VS-7375, an oral KRAS G12D inhibitor, posts a 50% second-line response rate in pancreatic cancer and heads to a first-line phase 3
In the phase 1/2 TARGET-D 101 trial, VS-7375 yielded responses in pancreatic, colorectal and lung cancers. In pancreatic cancer it produced 50% ORR in the second line and 35% in the third/fourth line, with a 6-month OS of 80%. A first-line phase 3 will randomize VS-7375 plus an EGFR inhibitor against VS-7375 plus chemotherapy. Clinicians question whether this data justifies a design with no chemotherapy-only control.
Discussed by: @Aiims1742, @jgong15
Sources cited: Cancer Network
NEONIPIGA 4-year follow-up in JAMA Oncology: one relapse in 32 patients with dMMR/MSI-H gastric/GEJ cancer reopens the gastrectomy question
Neoadjuvant nivolumab + ipilimumab produced durable survival with a single relapse across the cohort. All non-operated patients achieved a clinical complete response. The trial was single-arm, and the authors found no clear evidence of improved survival over surgery-alone series, though the outcomes support exploring organ preservation. The open questions are who still needs a gastrectomy and whether adjuvant nivolumab adds anything after a clinical complete response.
Key numbers: 4-yr OS 84.1% · 4-yr EFS 83.5% · pCR 59% (17/29) · Neoadjuvant grade 3/4 AEs 19%
Discussed by: @dr_yakupergun, @DrAllanPereira, @DraMartinezLago
Sources cited: JAMA Network
NCCN Pancreatic Adenocarcinoma v4.2026: tumour NGS with RNA sequencing for every treatment candidate, PAXG added, and no consensus on postoperative ctDNA
Tumour NGS with added RNA sequencing is now recommended for every candidate for anticancer therapy. Neoadjuvant PAXG is listed as useful in certain circumstances, based on an Italian phase 3 against mFOLFIRINOX (median EFS 16.0 vs 10.2 months, HR 0.63). Post-neoadjuvant resection decisions are now framed by biological response (RECIST, CA 19-9, clinical status) rather than vascular contact alone. Because the panel declined to recommend postoperative ctDNA, clinicians are debating whether to order it anyway and whether biological response is enough to operate on borderline-resectable patients.
Discussed by: @DrAllanPereira, @jgong15
A health-system-scale cachexia atlas in Nature Medicine puts a hazard ratio of ~3 on cachectic weight loss, with a prospective colorectal risk model
The Nature Medicine atlas covers 52K patients and includes prospective risk models for lung, colorectal and prostate cancer. It found a hazard ratio of ~3, meaning cancer patients with cachectic weight loss have triple the risk of death. Yet companies rarely even report weight changes in their clinical trials. Clinicians are asking whether GI oncology trials should be required to report weight and body-composition change as a routine endpoint.
Discussed by: @EladSharonMD, @CentralParkWMD
Sources cited: A health-system-scale, episode-resolved multimodal atlas of cancer cachexia (Nature Medicine, 2026) · AACR Journals · AACR Journals
Phase IIIb SIERRA: first-line durvalumab plus tremelimumab in poor-prognosis unresectable HCC (Child-Pugh B7/B8, ECOG PS 2, Vp4)
SIERRA enrolled 111 patients with poor-prognosis unresectable HCC (Child-Pugh B7/B8, ECOG PS 2, or Vp4). Investigators reported a favourable risk-benefit profile and manageable safety for STRIDE in these historically underrepresented populations. Responses were lowest in Child-Pugh B7/B8. The debate is whether a modest response rate and median OS from a single-arm phase IIIb justify STRIDE for patients excluded from HIMALAYA.
Key numbers: ORR 14.4% · Median OS 10.6 mo · Grade 3/4 PRAEs 19.8% · ORR CP B7/B8 6.8% · ORR ECOG PS 2 21.3%
Discussed by: @LorenzaRimassa, @hongjaechon
Sources cited: Elsevier
FFCD-AC real-world cohort: fluoropyrimidine- versus gemcitabine-based first line for metastatic recurrence after resected ampullary adenocarcinoma
In this real-world FFCD-AC analysis, response rates were similar between backbones. 5-FU-based therapy gave longer PFS but no OS difference. Absence of liver metastases was associated with better OS. Clinicians are debating whether recurrent ampullary adenocarcinoma is a fluoropyrimidine-first disease or whether histological subtype matters more than the backbone.
Key numbers: ORR 36.2% vs 32.0% · 5-FU PFS HR 0.53 · No liver mets OS HR 0.58
Discussed by: @LorenzaRimassa, @DraMartinezLago
Sources cited: European Journal of Cancer
🔥 Top Ranked Tweets
OncoAlert @OncoAlert
FDA NEWS🇺🇸 |
Atezolizumab approved with fluoropyrimidine + oxaliplatin for adjuvant Stage III dMMR #ColonCancer(adults & peds ≥2 yrs).
Subcutaneous Tecentriq Hybreza also approved (≥12 yrs, ≥40 kg).
Approval based on ATOMIC (NCT02912559): DFS HR 0.50 (95% CI 0.35–0.73; p=0.0001). 3-yr DFS ~86.3% vs 76.2%. Median DFS NR either arm.
@CathyEngMD, @BenWestphalen, @graokane, @NiuSanford, @AndresC27622123, @GillSharlene, @pashtoonkasi, @DrVilmaPBarcia, @Erman_Akkus, @GIMedOnc, @UOzkerim, @MarioBalsaMD, @p_ciracimd, @DraMartinezLago, @DaisukeKotani, @Aiims1742, @ARosen380, @realbowtiedoc, @KoheiShitara, @GaiaGriguolo, @scocmem
https://t.co/ecq8v9upC7
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OncoAlert @OncoAlert
RT @OncoAlert: FDA NEWS🇺🇸 |
Atezolizumab approved with fluoropyrimidine + oxaliplatin for adjuvant Stage III dMMR #ColonCancer(adults & peds ≥2 yrs).
Subcutaneous Tecentriq Hybreza also approved (≥12 yrs, ≥40 kg).
Approval based on ATOMIC (NCT02912559): DFS HR 0.50 (95% CI 0.35–0.73; p=0.0001). 3-yr DFS ~86.3% vs 76.2%. Median DFS NR either arm.
@CathyEngMD, @BenWestphalen, @graokane, @NiuSanford, @AndresC27622123, @GillSharlene, @pashtoonkasi, @DrVilmaPBarcia, @Erman_Akkus, @GIMedOnc, @UOzkerim, @MarioBalsaMD, @p_ciracimd, @DraMartinezLago, @DaisukeKotani, @Aiims1742, @ARosen380, @realbowtiedoc, @KoheiShitara, @GaiaGriguolo, @scocmem
https://t.co/ecq8v9upC7
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Gil Morgan, MD @weoncologists
RT @OncoAlert: FDA NEWS🇺🇸 |
Atezolizumab approved with fluoropyrimidine + oxaliplatin for adjuvant Stage III dMMR #ColonCancer(adults & peds ≥2 yrs).
Subcutaneous Tecentriq Hybreza also approved (≥12 yrs, ≥40 kg).
Approval based on ATOMIC (NCT02912559): DFS HR 0.50 (95% CI 0.35–0.73; p=0.0001). 3-yr DFS ~86.3% vs 76.2%. Median DFS NR either arm.
@CathyEngMD, @BenWestphalen, @graokane, @NiuSanford, @AndresC27622123, @GillSharlene, @pashtoonkasi, @DrVilmaPBarcia, @Erman_Akkus, @GIMedOnc, @UOzkerim, @MarioBalsaMD, @p_ciracimd, @DraMartinezLago, @DaisukeKotani, @Aiims1742, @ARosen380, @realbowtiedoc, @KoheiShitara, @GaiaGriguolo, @scocmem
https://t.co/ecq8v9upC7
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OncoAlert @OncoAlert
RT @sonbol_bassam: Positive interim PFS results for RYZ101 (²²⁵Ac-DOTATATE) in post-Lu177 GEP-NETs in ACTION-1. First Phase 3 data for an alpha RPT. Looking forward to the full results …
@OncoThor @OncoAlert
#NETs #GEPNETs
https://t.co/ZvZbm8COce
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OncoAlert @OncoAlert
RT @Markuseckstein3: 🚨 FDA, 8 October 2026: atezolizumab plus a fluoropyrimidine and oxaliplatin is approved for adjuvant treatment of stage III dMMR colon cancer (IV from age 2; subcutaneous atezolizumab/hyaluronidase from age 12 and ≥40 kg).
🧪 ATOMIC (Alliance A021502): 712 patients randomised at 312 sites, 355 vs 357. Six months of mFOLFOX6 with atezolizumab, followed by six months of atezolizumab alone, versus six months of mFOLFOX6 alone.
📉 3-year DFS: 86.3% vs 76.2%; HR 0.50 (95% CI 0.35–0.73), p<0.001. Median follow-up 40.9 months; 127 DFS events (46 vs 81).
📈 5-year OS estimates: 89.7% vs 87.9%; HR 0.90 (95% CI 0.55–1.47), p=0.68. Median OS follow-up 45.8 months; 31 vs 33 deaths.
⚠️ All-cause grade 3/4 AEs: 84.1% vs 71.9%; non-haematologic grade 3/4 AEs 69.4% vs 54.5%. Grade 5 events: 6 vs 2; two deaths in the atezolizumab arm were considered treatment-related.
🔬 Retrospective central review: 689 specimens submitted; 630 classified as dMMR, 42 as pMMR and 17 as inconclusive. Specimens were missing for 23 patients. The DFS benefit persisted in the 630 centrally confirmed dMMR cases.
1️⃣ The absolute DFS gain is 10.1 percentage points; the increase in all-cause grade 3/4 AEs is 12.2 points. These are different endpoints, measured over different time horizons. The estimated NNT is approximately 10 to prevent one recurrence-or-death event by three years. Treatment-attributed grade 3/4 AEs occurred in 72.5% vs 61.7%. Patients deserve the absolute benefit and the adverse-event burden, not HR 0.50 alone.
2️⃣ Overall survival remains immature, and an OS benefit is unproven. ATOMIC explicitly planned an OS analysis: approximately 163 deaths would provide 90% power to detect HR 0.60. Only 64 deaths had occurred. The current confidence interval permits meaningful benefit or harm; it does not establish equivalence. Longer follow-up is warranted, but a future OS advantage should not be promised. The demonstrated benefit is DFS.
3️⃣ Pathology is the gatekeeper, and the local–central discordance matters. Eligibility relied on local or site-selected reference-laboratory MMR immunohistochemistry. Central review subsequently classified 42 submitted tumours as pMMR. That does not establish which assessment was wrong, but it makes diagnostic quality assurance a concrete concern.
The prescribing information requires tumour dMMR status without mandating a specific assay, antibody panel or expert-adjudication workflow. Established CAP guidance, developed with AMP and endorsed by ASCO, already addresses MMR/MSI testing and difficult results. The implementation challenge is ensuring validated assays, adequate internal controls, reproducible interpretation and appropriate resolution of equivocal, heterogeneous or discordant findings. These decisions now determine eligibility for a year of adjuvant immunotherapy.
4️⃣ The paediatric extrapolation deserves context. The intravenous indication covers patients from age two; ATOMIC enrolled one adolescent. The label also draws on additional paediatric pharmacokinetic and safety data and extrapolates from similarity of disease course. Direct paediatric efficacy evidence remains very limited.
5️⃣ The label is broader than the trial. It permits "a fluoropyrimidine" with oxaliplatin, but ATOMIC tested only mFOLFOX6. Atezolizumab with CAPOX is an extrapolation without randomised evidence.
Adjuvant immunotherapy in dMMR colon cancer is a genuine advance. The next challenge is ensuring that the diagnostic pathway selecting patients is consistently quality-assured, and that discussions of benefit distinguish improved DFS from an as-yet unproven OS advantage.
🔗 FDA approval: https://t.co/yRMu5TEuq8
🔗 ATOMIC publication: https://t.co/T9lAOmGT6a
@ASCO @PathSoc @OncoAlert @Histo_Journal @onkowissen @imedverse @NEJM
#oncology #PrecisionOncology #pathtwitter #ColonCancer #dMMR
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OncoAlert @OncoAlert
RT @drenriquegrande: 🚨 Exciting times for the #NET community!
Positive Phase III #ACTION1 results with ²²⁵Ac-DOTATATE after progression on ¹⁷⁷Lu!
A major milestone for alpha-emitting radioligand therapy and potentially a new chapter in #NET treatment sequencing.
But why does this matter? 🧵👇
🎯 Same target, different radiation!
🔵 ¹⁷⁷Lu (Lutetium): Beta emitter, longer tissue range, lower linear energy transfer (LET).
🔴 ²²⁵Ac (Actinium): Alpha emitter, very short range, much higher LET and potentially more lethal DNA double-strand damage.
Not simply a stronger lutetium!
📊 #ACTION1 reports significantly improved PFS versus standard-of-care options in SSTR+ GEP-NETs progressing after ¹⁷⁷Lu.
Very encouraging! 👏
But let's see the full data: HR, absolute PFS benefit, long-term toxicity, OS and quality of life.
And important questions remain:
⚠️ Cumulative renal and bone marrow toxicity
🏭 Isotope production and availability
🚚 Manufacturing, logistics and equitable access
🔬 Optimal sequencing and patient selection
🌍 Perfect timing for #ESMO26 in Madrid!
📅 Sunday, October 25
🕝 14:45–16:15
📍 Leon Auditorium, Hall 4
Join us for our educational session on radioligand therapy in advanced NETs, with @Ja_Capdevila and an outstanding international faculty! @OncoThor @RachelRiechelm2
Looking forward to discussing how we can translate these advances into better outcomes for our patients.
See you all at #ESMO26 in Madrid! 🇪🇸🤝
@myESMO @Netespana @_SEOM
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CancerNetwork® @CancerNetwrk
RYZ101 (225Ac-DOTATATE) demonstrated significant improvement in PFS vs investigator’s choice of standard of care in SSTR+ GEP-NETs that progressed following lutetium-177–based therapy.
More 👉 https://t.co/daqCfeCEh1
#gicsm #oncology #cancer https://t.co/JfKwM38Lmz
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Nieves Martinez Lago MD PhD @DraMartinezLago
FDA NEWS🇺🇸 |
Atezolizumab approved with fluoropyrimidine + oxaliplatin for adjuvant Stage III dMMR #ColonCancer(adults & peds ≥2 yrs).
Subcutaneous Tecentriq Hybreza also approved (≥12 yrs, ≥40 kg).
Approval based on ATOMIC (NCT02912559): DFS HR 0.50 (95% CI 0.35–0.73; p=0.0001). 3-yr DFS ~86.3% vs 76.2%. Median DFS NR either arm👇
[Quoting @OncoAlert: FDA NEWS🇺🇸 |
Atezolizumab approved with fluoropyrimidine + oxaliplatin for adjuvant Stage III dMMR #ColonCancer(adults & peds ≥2 yrs).
Subcutaneous Tecentriq Hybreza also approved (≥12 yrs, ≥40 kg).
Approval based on ATOMIC (NCT02912559): DFS HR 0.50 (95% CI 0.35–0.73; p=0.0001). 3-yr DFS ~86.3% vs 76.2%. Median DFS NR either arm.
@CathyEngMD, @BenWestphalen, @graokane, @NiuSanford, @AndresC27622123, @GillSharlene, @pashtoonkasi, @DrVilmaPBarcia, @Erman_Akkus, @GIMedOnc, @UOzkerim, @MarioBalsaMD, @p_ciracimd, @DraMartinezLago, @DaisukeKotani, @Aiims1742, @ARosen380, @realbowtiedoc, @KoheiShitara, @GaiaGriguolo, @scocmem
https://t.co/ecq8v9upC7]
🔖 3 ❤️ 15 🔁 7 👁 1,233
Journal of Clinical Oncology @JCO_ASCO
Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Living Guideline, Version 2026.1.2.
Read the full article. https://t.co/iCsUiaKPYr
🔖 5 ❤️ 3 🔁 3 👁 1,444
Hong Jae Chon @hongjaechon
RT @Erman_Akkus: Pembrolizumab plus gemcitabine and cisplatin for advanced biliary tract cancer: longer-term follow-up from the randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-966 trial
https://t.co/paNeuRvhrZ
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The ASCO Post @ASCOPost
🧬 In the phase III RELIGHT trial, retlirafusp alfa + CAPOX improved median overall survival vs chemotherapy alone in patients with advanced HER2-negative #GastricCancer: 15.8 vs 11.2 months (HR = 0.66).
🔹Lin Shen, MD | @JCO_ASCO
Explore the findings ➡️ https://t.co/tkWzjkaXE0 https://t.co/3Vxa8SAZBq
🔖 7 ❤️ 18 🔁 7 👁 2,105
Ronan Hsieh, MD, MS @ronanhsieh
RT @DraMartinezLago: FDA NEWS🇺🇸 |
Atezolizumab approved with fluoropyrimidine + oxaliplatin for adjuvant Stage III dMMR #ColonCancer(adults & peds ≥2 yrs).
Subcutaneous Tecentriq Hybreza also approved (≥12 yrs, ≥40 kg).
Approval based on ATOMIC (NCT02912559): DFS HR 0.50 (95% CI 0.35–0.73; p=0.0001). 3-yr DFS ~86.3% vs 76.2%. Median DFS NR either arm👇
🔖 3 ❤️ 15 🔁 7 👁 1,234
Elad Sharon @EladSharonMD
RT @OncoDailyGI: Major Milestone in Colon Cancer: FDA Approves Atezolizumab Adjuvant Combination – Alliance for Clinical Trials in Oncology
@FASinicropeMD @ALLIANCE_org
https://t.co/cXQzBnqmUT https://t.co/3DrufIehQ6
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Elad Sharon @EladSharonMD
RT @oncologytube: VIDEO: Atezolizumab for resected stage III dMMR colon cancer — add it to chemo? FDA approved Oct 8, 2026: DFS HR 0.50 🧬
👉 https://t.co/IOue5PhbXP
🔹 ATOMIC (N=712): atezolizumab + mFOLFOX6, then atezolizumab alone, vs mFOLFOX6
🔹 3-yr DFS 86.3% vs 76.2% (HR 0.50; 95% CI 0.35–0.73)
🔹 Label: with a fluoropyrimidine + oxaliplatin; grade 3–4 AEs 84.1% vs 71.9%; OS not mature
Check MMR status before choosing adjuvant therapy.
@FASinicropeMD @EileenMOReilly @ilyassahinMD @dr_yakupergun @CathyEngMD @smitha42 @GIcancerDoc @MyriamChalabi @BijoyTelivala @RenoHemonc @dr_alhashem @ArndtVogel @GillSharlene @ryanhuey @OncoThor @DrRishabhOnco @ChandrakanthMv @GlopesMd @YannickBuccella @KaiKeenShiu @KristenCiombor @KimmieNgMD @marklewismd @VanMorrisMD @RonaYaeger @benweinbergmd @agrothey @aakonc @UGrewalMD @GIMedOnc @jgong15 @ShaalanBeg @BGriebMD @realbowtiedoc @Erman_Akkus
#crcsm #ColonCancer #dMMR #Atezolizumab #ATOMIC #GIonc
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gilberto lopes @GlopesMd
RT @GlopesMd: A major advance in stage III dMMR colon cancer.
FDA approves adjuvant atezolizumab + chemotherapy following the phase III ATOMIC trial.
3-year DFS:
✅ 86.3% vs 76.2%
📉 HR 0.50 (95% CI 0.35–0.73) https://t.co/PX1gpkmPdw
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🧪 Newly Recruiting Trials
6 trials (3 phase II, 3 phase I) opened this week, testing telisotuzumab adizutecan plus gemcitabine, histotripsy plus durvalumab, stereotactic body radiation therapy, ABBV-253, LTZ-232 and biomarker-matched targeted therapy selection
Phase 2 · AbbVie · telisotuzumab adizutecan plus gemcitabine · Mississippi · CT.gov ↗
Phase 2 · University of Wisconsin, Madison · histotripsy plus durvalumab · Wisconsin · CT.gov ↗
Phase 2 · Mark Bernard · stereotactic body radiation therapy · Kentucky · CT.gov ↗
Phase 1 · AbbVie · ABBV-253 · Michigan, North Carolina, Texas · CT.gov ↗
Phase 1 · LTZ Therapeutics, Inc. · LTZ-232 · Arizona · CT.gov ↗
Phase 1 · M.D. Anderson Cancer Center · biomarker-matched targeted therapy selection · Texas · CT.gov ↗
Open all 6 on the trials page →
Agent descriptions from the NCI Thesaurus.
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