GI Oncology Weekly — Issue 13

This week’s calls — 5 readouts · 1 to act on · ~7 min read. Tap any row to jump.

ATOMIC FDA approves adjuvant atezolizumab plus fluoropyrimidine–oxaliplatin for resected stage III dMMR colon cancer Practice-shaping RATIONALE-306 Tislelizumab plus chemotherapy in first-line advanced ESCC at a minimum 36 months: OS HR 0.70, and 15% progression-free at three years Worth watching KEYNOTE-966 Pembrolizumab plus gemcitabine–cisplatin in advanced biliary tract cancer at a median 36.6 months: OS HR 0.86, identical response rates, longer responses Worth watching CLDN18.2 dynamics In 155 paired gastric/GEJ biopsies, CLDN18.2 status changed after systemic therapy in 84.5%; one in five negatives became positive Worth watching Afatinib + cetuximab Dual EGFR blockade in chemorefractory RAS wild-type mCRC: randomised phase II negative, more toxic, with a day-14 CTC signal On the radar

This week · 5 readouts

The Verdicts

Every trial that matters this week, distilled to a single call — act on it, watch it, or keep it on the radar.

Practice-shaping Colon · adjuvant, dMMR

ATOMIC

This is the week's practice change. Adding atezolizumab to adjuvant FOLFOX halved the risk of recurrence or death in resected stage III dMMR colon cancer, and the treatment is now on label. The FDA notice reports no overall survival data, so the approval rests on disease-free survival. The workflow consequence matters as much as the drug: MMR status has to be known before adjuvant therapy starts, not filed afterwards as a prognostic footnote.

· DFS HR 0.50 (95% CI 0.35–0.73), p = 0.0001· median DFS not reached in either arm· n = 712 (711 adults + 1 pediatric)· OS not reported in the FDA notice

Go deeper

On October 8, 2026, the FDA approved atezolizumab (Tecentriq) in combination with a fluoropyrimidine and oxaliplatin as adjuvant treatment for adult and pediatric patients two years and older with resected stage III mismatch repair–deficient (dMMR) colon cancer; the subcutaneous formulation, atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza), was approved alongside it for patients 12 and older weighing at least 40 kg. Efficacy came from ATOMIC/ML39057 (NCT02912559), a multicentre, randomised, open-label, active-controlled trial in 711 adults and one pediatric patient after complete resection, randomised 1:1 to atezolizumab plus mFOLFOX6 for 12 cycles followed by six months of atezolizumab monotherapy, or mFOLFOX6 alone for 12 cycles. Investigator-assessed disease-free survival was the major efficacy outcome: HR 0.50 (95% CI 0.35–0.73; p = 0.0001), with median DFS not reached in either arm. The FDA notice gives no overall survival data, so the approval rests on halving the risk of recurrence or death. The recommended adult dose is 840 mg every two weeks, 1200 mg every three weeks, or 1680 mg every four weeks with chemotherapy for six months, then single-agent atezolizumab for six months. For practice, this makes dMMR testing on every resected stage III colon cancer a treatment decision rather than a prognostic footnote. Full daily entry →

U.S. Food and Drug Administration · approval based on the randomised phase 3 ATOMIC trial Debate on X →

Worth watching Esophagus · first-line advanced ESCC

RATIONALE-306

First-line PD-1 plus chemotherapy is already standard in ESCC, so this does not change practice. What it adds is the shape of the benefit: the overall survival lead holds at three years, and 15% of patients are still progression-free against 3% with chemotherapy alone. That tail is what PD-1 blockade was supposed to deliver. The next question is selection: who ends up in that 15%.

· mOS 17.2 vs 10.6 mo (HR 0.70, 95% CI 0.59–0.80)· 3-yr progression-free 15.0% vs 2.9%· minimum follow-up 36.0 mo· n = 649 randomised· no new safety signals

HR 0.7 ↓ 30% risk of death 95% CI 0.59–0.80 · Δ +6.6 mo median 3-yr progression-free 15.0% vs 2.9%

Survival over time · schematic — OS*

Tislelizumab + chemoPlacebo + chemo

Go deeper

RATIONALE-306 randomised 649 patients with unresectable advanced or metastatic esophageal squamous cell carcinoma 1:1 to tislelizumab 200 mg or placebo, each with investigator-chosen chemotherapy, in the first-line setting. The primary OS benefit was reported at a minimum follow-up of about 15 months; this exploratory analysis extends minimum follow-up to 36.0 months. Overall survival remained improved in all patients, 17.2 versus 10.6 months (HR 0.70, 95% CI 0.59–0.80). At three years 15.0% of patients on tislelizumab plus chemotherapy had not progressed, against 2.9% on placebo plus chemotherapy. No new safety signals emerged, and median time to deterioration of physical functioning was not reached with tislelizumab versus 18.8 months with placebo. Full daily entry →

Nature Communications · randomised phase 3, exploratory 3-year follow-up

Worth watching Biliary · first-line advanced

KEYNOTE-966

This is the second three-year IO update of the week, and it tells a similar story more quietly. The survival benefit holds (HR 0.86), but response rates were identical in both arms, so the gain comes from how long responses last. The curves narrow by 36 months (13% vs 11% alive). The analysis is descriptive and the data cutoff was November 2023. It confirms the regimen; it does not tell us who the long-term survivors are, and that is the question that matters now.

· mOS 12.7 vs 10.9 mo (HR 0.86, 95% CI 0.75–0.98)· 24-mo OS 25% vs 19%· 36-mo OS 13% vs 11%· ORR 29% vs 29%· median DOR 8.3 vs 6.9 mo· n = 1,069· descriptive update, no alpha allocated

HR 0.86 ↓ 14% risk of death 95% CI 0.75–0.98 · Δ +1.8 mo median 36-mo OS 13% vs 11%

Survival over time · schematic — OS*

Pembrolizumab + gem/cisPlacebo + gem/cis

Go deeper

KEYNOTE-966 randomised 1,069 patients with previously untreated advanced biliary tract cancer to pembrolizumab or placebo plus gemcitabine and cisplatin. This update reports a median follow-up of 36.6 months, 11 months beyond the final analysis. The OS benefit held: HR 0.86 (95% CI 0.75–0.98), median OS 12.7 vs 10.9 months, 24-month OS 25% vs 19%, and 36-month OS 13% vs 11%. PFS also favoured pembrolizumab (HR 0.85, 95% CI 0.75–0.97). ORR was identical at 29% in both arms, but responses lasted longer with pembrolizumab: median duration 8.3 vs 6.9 months, and 18% vs 7% of responders were still responding at 24 months. Grade 3–4 treatment-related adverse events were 70% vs 69%, with no new treatment-related deaths. Two caveats: the analysis is descriptive, since no alpha was allocated, and the data cutoff was November 2023. Full daily entry →

eClinicalMedicine · randomised phase 3, 3-year follow-up

Worth watching Gastric · CLDN18.2 biomarker

CLDN18.2 dynamics

A CLDN18.2 result goes out of date. After systemic therapy, one in five baseline-negative tumours became positive and more than a quarter of positives became negative, whether or not immunotherapy was given. This is a retrospective study, but it points to a simple step: before a later-line CLDN18.2-directed decision, consider re-testing instead of relying on the diagnostic biopsy.

· CLDN18.2-positive 34.84% before vs 39.35% after therapy, p < .001· negative → positive 21.78%· positive → negative 27.78%· any change 84.52%· n = 155 paired samples

CLDN18.2-positive tumours, before vs after systemic therapy · 0–100% scale

34.84%Before therapy

39.35%After therapy

050100%

Go deeper

Investigators retrospectively scored claudin 18.2 by immunohistochemistry on paired tumour samples taken before and after systemic therapy in 155 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, using the zolbetuximab-era definition of positivity: at least 75% of viable tumour cells with moderate-to-strong (2+/3+) membranous staining. Positivity rose from 54 patients (34.84%) before treatment to 61 (39.35%) after (p < .001). Among baseline-negative patients, 56.44% showed increased expression and 22 (21.78%) converted to positive; among baseline-positive patients, 64.81% showed decreased expression and 15 (27.78%) converted to negative. Conversion rates did not differ significantly between chemotherapy alone (n = 25) and chemotherapy plus immunotherapy (n = 130; p = .45). Overall, 131 patients (84.52%) showed some change in CLDN18.2 expression, which led the authors to recommend reassessing status before starting CLDN18.2-targeted therapy. Full daily entry →

Cancer · retrospective paired-biopsy cohort Debate on X →

On the radar Colorectal · refractory RAS wild-type

Afatinib + cetuximab

This negative trial is worth knowing. Adding afatinib to cetuximab did not reach its efficacy bar in refractory RAS wild-type mCRC, and it added toxicity, including two grade 5 events. Doubling up on EGFR does not rescue EGFR resistance. The part to keep is the circulating tumour cell readout: a fall by day 14 tracked with survival and response.

· 6-mo non-progression 18% (95% CI 8–31) vs 30% minimum success, primary endpoint not met· ORR 26%· mPFS 4.1 mo· mOS 13.6 mo· grade ≥3 toxicity 76% vs 64%· n = 75 randomised 2:1

Go deeper

This multicentre, open-label, non-comparative randomised Phase II trial assigned 75 patients with chemorefractory RAS wild-type mCRC 2:1 to afatinib 40 mg/day plus cetuximab (n=51) or to cetuximab alone (n=24) as an internal control. Crossover to afatinib was allowed at progression. The primary endpoint was not met: only 9 patients (18%, 95% CI 8–31) in the combination arm were progression-free at 6 months, against a minimum success rate of 30%. In the combination arm, ORR was 26%, median PFS 4.1 months and median OS 13.6 months. Grade ≥3 toxicity occurred in 76% vs 64% of patients, with two grade 5 events in the combination arm (sudden death and hypoglycaemia). High baseline circulating tumour cell (CTC) counts and a fall in CTCs by day 14 correlated with OS and ORR. Full daily entry →

Clinical Colorectal Cancer · randomised non-comparative phase II (UNICANCER)

* Survival curves are illustrative — modeled from each trial’s reported median and hazard ratio (assuming exponential survival), not the published Kaplan–Meier curves.

The take

Two first-line immunotherapy trials reached three years of follow-up this week, and both say the same thing: the benefit of PD-1 blockade in GI cancers sits in a minority of patients whose disease stays controlled for a long time.

RATIONALE-306: 15% progression-free at three years with tislelizumab, versus 3% without.
KEYNOTE-966: identical response rates, but responses lasted longer and 18% vs 7% of responders were still responding at two years.
ATOMIC moves the same drug class into the curative setting for the clearest biomarker we have, dMMR, and it is now on label.

The practical step is ATOMIC: test MMR on every resected stage III colon cancer before adjuvant therapy starts. The scientific gap is the other two trials. We can now show that a durable tail exists in ESCC and biliary cancer, but we still cannot tell a patient in advance whether they will be in it. Selection is the next trial.

GI Oncology Weekly · curated by Dr. Allan Pereira, Moffitt Cancer Center. Educational summaries for practising oncologists — not medical advice; verify against primary sources before acting.

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