GI Oncology Weekly — Issue 1

This week’s calls — 5 readouts · 2 to act on · ~4 min read. Tap any row to jump.

COMPETE PRRT nearly doubles PFS vs everolimus Practice-shaping JUPITER-06 (final OS) Toripalimab + chemo sustains OS in ESCC Practice-shaping PICC-2 Adding celecoxib lifts pCR to 89% in dMMR CRC Worth watching eNRGy (zenocutuzumab) First targeted activity in NRG1-fusion biliary cancer Worth watching CAIRO6 Perioperative chemo adds nothing over upfront CRS-HIPEC 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 Neuroendocrine

COMPETE

In advanced, progressive somatostatin-receptor-positive GEP-NETs, peptide receptor radionuclide therapy outperformed everolimus on progression-free survival by blinded central review — the first head-to-head phase 3 to establish PRRT over a targeted oral agent. A clear signal to move PRRT up the sequence in SSTR-positive disease.

Go deeper

COMPETE randomized 309 patients (2:1) with advanced, progressive, somatostatin-receptor-positive grade 1-2 gastroenteropancreatic neuroendocrine tumours to peptide receptor radionuclide therapy ([177Lu]Lu-edotreotide, up to four cycles) versus everolimus 10 mg/day. Median PFS by blinded central review was significantly longer with PRRT: 23.9 vs 14.1 months (stratified HR 0.67, 95% CI 0.48-0.95; p=0.022). PRRT was also better tolerated — grade 3-4 treatment-related adverse events occurred in 18% vs 40%, with no treatment-related deaths in either arm. The trial adds a second randomized dataset (after NETTER-2) supporting PRRT in earlier lines and directly informs how we sequence radioligand versus targeted therapy in GEP-NETs. Full daily entry →

Survival over time · schematic — PFS*

[177Lu]Lu-edotreotide (PRRT)Everolimus 10 mg/day

· median PFS 23.9 vs 14.1 mo· HR 0.67 (0.48–0.95)

HR 0.67 ↓ 33% risk of progression 95% CI 0.48–0.95 · Δ +9.8 mo median

The Lancet · 2 July 2026 · phase 3, n=309 Debate on X →

Practice-shaping Esophageal

JUPITER-06 (final OS)

The final overall-survival analysis confirms a durable first-line benefit for toripalimab plus chemotherapy in advanced esophageal squamous-cell carcinoma — and, more provocatively, a genomic scheme (ccTMB/EGIC) that out-predicts PD-L1 for who benefits.

· median OS 17.7 vs 12.9 mo· HR 0.72 (0.58–0.88)· P=0.002· 3-yr OS 29.7 vs 19.9%

HR 0.72 ↓ 28% risk of death 95% CI 0.58–0.88 · Δ +4.8 mo median 3-yr OS 29.7% vs 19.9%

Survival over time · schematic — OS*

Toripalimab + paclitaxel/cisplatinPlacebo + paclitaxel/cisplatin

Go deeper

The final overall survival analysis of JUPITER-06, the Phase III trial of first-line toripalimab plus paclitaxel/cisplatin (TP) versus placebo + TP in 514 patients with treatment-naive advanced esophageal squamous-cell carcinoma (ESCC), confirms a durable survival benefit: median OS 17.7 vs 12.9 months (HR 0.72, 95% CI 0.58–0.88, P=0.002), with 3-year OS of 29.7% vs 19.9%. The more important message is biomarker-driven. Neither PD-L1 expression nor conventional TMB correlated with OS benefit; instead, two prespecified genomic tools — copy-number-corrected TMB (ccTMB) and the esophageal cancer genome-based immuno-oncology classification (EGIC) — robustly stratified long-term survivors. Exploratory analysis of 486 sequenced tumors linked loss-of-function SWI/SNF alterations to improved OS and gain-of-function cell-cycle/WNT alterations to reduced benefit, nominating CDK4/6 and PORCN inhibitors as rational combination partners to overcome resistance. Full daily entry →

Annals of Oncology · 2026;37(7):986–998 · phase 3, n=514

Worth watching Colorectal · dMMR/MSI-H

PICC-2

In locally advanced dMMR/MSI-H colorectal cancer, adding the COX-2 inhibitor celecoxib to neoadjuvant toripalimab pushed pathological complete response to 89% — a striking, cheap add-on. Phase 2 and needs confirmation, but the effect size is hard to ignore.

· pCR 89% (49/55) vs 69% (38/55)· +19 pts (95% CI 4–34)· p=0.014

Pathological complete response · 0–100% scale

89%Toripalimab + celecoxib

69%Toripalimab alone

050100%

Go deeper

This open-label, multicentre phase 2 trial randomized 110 patients with dMMR/MSI-H locally advanced colorectal cancer to neoadjuvant toripalimab plus the COX-2 inhibitor celecoxib versus toripalimab alone before surgery. The combination raised pathological complete response to 89% (49/55) versus 69% (38/55) — a 19-point absolute gain (95% CI 4-34, p=0.014). Grade 3 treatment-related adverse events were uncommon in both arms, with no grade 4/5 events reported. PICC-2 suggests a cheap, oral partner can push already-impressive neoadjuvant immunotherapy pCR rates in dMMR colon cancer even higher, strengthening the organ-preservation conversation. Full daily entry →

Lancet Oncology · 1 July 2026 · phase 2, n=110 Debate on X →

Worth watching Cholangiocarcinoma · NRG1

eNRGy (zenocutuzumab)

The cholangiocarcinoma cohort of the eNRGy basket shows the first targeted activity in NRG1 fusion-positive biliary cancer — a vanishingly rare subtype with no prior on-target option. Worth testing for, worth having in the toolkit.

· ORR 36.8% (95% CI 16.3–61.6)· CBR 57.9%· phase 2, n=22

Go deeper

The single-arm Phase 2 eNRGy basket reported the cholangiocarcinoma cohort: 22 previously treated patients with NRG1 fusion-positive advanced disease (all intrahepatic where subtype was known) received the HER2xHER3 bispecific antibody zenocutuzumab 750 mg IV every 2 weeks. Among 19 efficacy-evaluable patients, ORR was 36.8% (95% CI 16.3-61.6), clinical benefit rate 57.9%, median duration of response 7.4 months and median PFS 9.2 months. Toxicity was mostly grade 1-2 (diarrhea, fatigue, nausea) with a single grade 3 event and no AE discontinuations. NRG1 fusions are rare (well under 1% of biliary cancers), but this is the first credible targeted signal in the subtype and a concrete argument for RNA-based fusion testing across advanced cholangiocarcinoma. Full daily entry →

Journal of Clinical Oncology · 1 July 2026 · phase 2, n=22 Debate on X →

On the radar Colorectal · peritoneal

CAIRO6

The most instructive negative of the week: adding perioperative systemic therapy to CRS-HIPEC for resectable colorectal peritoneal-only metastases did not improve overall survival, and cost more morbidity. A useful de-escalation signal — upfront surgery remains reasonable.

· median OS 44 vs 39 mo· HR 0.85 (0.62–1.15)· p=0.28 (NS)· 90-day major morbidity 36% vs 26%

HR 0.85 No significant difference 95% CI 0.62–1.15 · Δ +5 mo median · p=0.28

Survival over time · schematic — OS*

Perioperative chemo + CRS-HIPECUpfront CRS-HIPEC alone

Go deeper

CAIRO6 randomized 358 patients with resectable colorectal peritoneal-only metastases to perioperative systemic therapy plus CRS-HIPEC versus upfront CRS-HIPEC alone. Median overall survival was 44 versus 39 months (HR 0.85, 95% CI 0.62-1.15, p=0.28) — no significant benefit — while major 90-day morbidity was higher with perioperative chemotherapy (36% vs 26%). This is an important negative result: it argues against reflexively giving perioperative chemotherapy to all comers with resectable peritoneal disease, and refocuses the decision on patient selection rather than blanket application. Full daily entry →

Lancet Oncology · 1 July 2026 · phase 3, n=358 Debate on X →

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

Regulatory · what to watch

Recent Regulatory Approvals

Regulatory milestones from the week, with the practice-relevant detail.

EU APPROVAL

Trastuzumab deruxtecan (Enhertu)

First tumour-agnostic HER2-directed therapy approved in Europe: T-DXd monotherapy for pretreated, unresectable or metastatic HER2-positive (IHC 3+) solid tumours with no satisfactory alternative. HER2 testing now matters across GI tumour types, not just gastric.

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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