📬 GI Cancer Intelligence Digest — Week 2026-W37

FDA approval of daraxonrasib for metastatic pancreatic adenocarcinoma dominates GI discussion alongside its $39,800/month price tag, while NEST phase 2 and mature BOT/BAL data push immunotherapy into MSS colorectal cancer, adagrasib plus cetuximab loses its accelerated approval, and DEEPER's final analysis, GlutaPanc, TALENTACE/EMERALD-3 and the BioNTech vaccine halt round out the week.

⚡ TL;DR

📄 Publications

Long-Term Survival Outcomes of Modified-FOLFOXIRI Plus Cetuximab Versus Bevacizumab in RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Final Analysis of the DEEPER Trial. — No differences in PFS and OS in the per-protocol set
L-Glutamine in combination with first-line gemcitabine and nab-paclitaxel in advanced pancreatic ductal adenocarcinoma: an open-label, single-arm, phase 1 GlutaPanc trial. — Single-arm phase 1 in 16 treatment-naive advanced pancreatic cancer patients

🐦 Twitter / 🦋 Bluesky

Update: daraxonrasib is now FDA approved and in the clinic, and the conversation has shifted from the survival curve to a $39,800-a-month price and a RAS-agnostic label — FDA approved daraxonrasib for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy
FDA withdraws the accelerated approval of adagrasib plus cetuximab in KRAS G12C colorectal cancer after KRYSTAL-10 misses both primary endpoints — The accelerated approval was officially withdrawn September 1 after KRYSTAL-10 failed to confirm benefit
HERIZON-GEA-01 second interim analysis: zanidatamab plus chemotherapy improves overall survival versus trastuzumab plus chemotherapy in first-line HER2-positive gastroesophageal adenocarcinoma — The second interim analysis showed zanidatamab plus chemotherapy significantly improved overall survival versus trastuzumab plus chemotherapy as first-line treatment for HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma
GlutaPanc phase 1 in Nature Cancer: adding FDA-approved high-dose L-glutamine to gemcitabine plus nab-paclitaxel in first-line metastatic pancreatic cancer — The phase 1 GlutaPanc trial paired FDA-approved high-dose L-glutamine with first-line gemcitabine/nab-paclitaxel in metastatic pancreatic cancer
Gastrectomy after systemic therapy in cStage IVB gastric cancer: 3-year OS 65% in 121 selected patients — In 121 selected patients undergoing gastrectomy after systemic therapy for cStage IVB gastric cancer, 3-year OS was 65%, with 76% versus 43% in oligometastatic versus non-oligometastatic disease

Full details below ↓

📄 What's Being Published

Manuscripts:

Extended Follow-Up of Botensilimab Plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer Without Active Liver Metastases. — Schlechter Benjamin L et al., Clin Cancer Res

As of December 13, 2025, 123 patients were treated at a median follow-up of 20.2 months (range, 0.7–62.3). The overall response rate was 21% (95% CI, 14–29), median PFS was 4.0 months (95% CI, 2.8–4.1), and median OS was 21.2 months (95% CI, 16.2–23.8), with a 36-month OS of 33% (95% CI, 24–43). Efficacy was consistent in late-line-exposed patients (n=37), where ORR was 22% (95% CI, 10–38) and median OS was 16.2 months (95% CI, 9.7–31.3); the most common treatment-related adverse events were diarrhea (39%; grade ≥3, 8%) and fatigue (37%; grade ≥3, 2%).

Clinical bottom line: In microsatellite-stable metastatic colorectal cancer without active liver metastases, botensilimab plus balstilimab produces a 21% response rate and 21.2-month median overall survival after a median of three prior lines, making the no-liver-metastasis population the setting in which checkpoint blockade should be tested in randomized trials.

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Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment, and follow-up of patients with hepatocellular carcinoma. — Tan C K et al., ESMO Open

The ESMO Clinical Practice Guidelines for hepatocellular carcinoma published in May 2025 were adapted in August 2025, using previously established standard methodology, to produce Pan-Asian adapted ESMO consensus guidelines for Asian patients with HCC. Voting was based on scientific evidence and was independent of current treatment practices, drug access restrictions, and reimbursement decisions across the different regions of Asia. The guidelines draw attention to the disparity in drug approvals and reimbursement strategies between those regions.

Clinical bottom line: The Pan-Asian adaptation of the ESMO hepatocellular carcinoma guideline separates what the evidence supports from what each Asian country can actually reimburse, and clinicians in the region should read the access commentary as carefully as the recommendations.

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L-Glutamine in combination with first-line gemcitabine and nab-paclitaxel in advanced pancreatic ductal adenocarcinoma: an open-label, single-arm, phase 1 GlutaPanc trial. — Gong Jun et al., Nat Cancer

This single-arm phase 1 trial enrolled 16 treatment-naive patients with advanced pancreatic cancer to assess FDA-approved L-glutamine combined with gemcitabine and nab-paclitaxel. The combination induced tumor shrinkage in 94% of subjects, with a best overall response rate of 44% including 12.5% complete responses, a median PFS of 8.5 months (95% CI, 6–NR), and a median OS of 22 months (95% CI, 11–NR). The grade ≥3 treatment-related adverse event rate was 66.7%, primarily attributable to the gemcitabine/nab-paclitaxel backbone.

Clinical bottom line: High-dose oral L-glutamine can be safely combined with full-dose gemcitabine and nab-paclitaxel, and the response and survival signal in these 16 patients is strong enough to justify a randomized trial, but a single-arm phase 1 compared with historical controls cannot establish benefit.

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🔗 Also discussed on social media →

Diagnostic pitfalls and unmet needs in neuroendocrine neoplasms: The added value of collegial expert pathology review through the national TENpath network. — Tihy Matthieu et al., Eur J Cancer

Of 3,239 cases received by ENDOCAN-TENpath, 126 (3.9%) were submitted to third-reading review by 22 of 33 network pathologists, with a median turnaround of 20 days; consensus or majority diagnosis was reached in 102 cases (81%). Critically, 20/46 presumed neuroendocrine neoplasms were reclassified as non-neuroendocrine malignancies and 5/25 presumed adenocarcinomas were reclassified as NENs, fundamentally altering treatment strategy. Additionally, 32/42 ambiguous high-grade NENs were definitively classified as tumor or carcinoma, directly determining the first-line chemotherapy regimen.

Clinical bottom line: Difficult neuroendocrine neoplasm pathology should be routed to a collegial expert panel rather than a single second opinion, because in this French network roughly one in four reviewed cases had its lineage or grade reassigned in a way that changed the treatment plan.

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Long-Term Survival Outcomes of Modified-FOLFOXIRI Plus Cetuximab Versus Bevacizumab in RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Final Analysis of the DEEPER Trial. — Sunakawa Yu et al., J Clin Oncol

In the per-protocol set, there were no differences in PFS or OS between modified-FOLFOXIRI plus cetuximab and bevacizumab. In the subgroup of patients with RAS/BRAF wild-type left-sided tumors, median PFS was longer with cetuximab than with bevacizumab (14.8 vs 11.9 months; HR, 0.71 [95% CI, 0.52–0.97]; P=.029), and median OS was 50.2 months versus 40.2 months (HR, 0.74 [95% CI, 0.53–1.05]). Exploratory analyses showed longer OS with cetuximab in male patients (HR, 0.59; P=.016) and in patients with extrahepatic disease (HR, 0.60; P=.014).

Clinical bottom line: The full DEEPER final analysis is now published and discussion has turned from the left-sided subgroup numbers to toxicity and whether triplet plus anti-EGFR is defensible at all, with clinicians noting the overall population showed no PFS or OS difference.

Read full article →

🗂 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).

Update: daraxonrasib is now FDA approved and in the clinic, and the conversation has shifted from the survival curve to a $39,800-a-month price and a RAS-agnostic label

The FDA approved daraxonrasib for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy — wording that drew comment for centering physician autonomy and patient needs. In the pivotal phase 3 RASolute 302 trial, median overall survival was 13.2 months with daraxonrasib versus 6.7 months with standard chemotherapy, and patients on the experimental arm were also more likely to receive subsequent-line therapy; one clinician reported sending 15 back-to-back prescriptions to a specialty pharmacy in a single day. At the same time, a reported price of $39,800 USD per month has focused attention on access, and the RAS-agnostic indication — covering patients regardless of RAS mutation status — drew debate relative to ESMO's restriction of daraxonrasib to RAS G12-mutated disease. A note of caution ran alongside the enthusiasm: in RASolute 302's control arm, 55/214 (26%) of patients withdrew or deteriorated on treatment, raising concerns about attrition in future first-line trials, and clinicians observed that RASolute 302 has not established how to build curative-intent strategies around RAS inhibition or how post-RAS resistance manifests.

Discussed by: @EladSharonMD, @OncoAlert, @EladSharonMD, @EladSharonMD, @jgong15, @neerajaiims, @pashtoonkasi, @VivekSubbiah, @DrMirallas, @PatrickHwuMD, @NiuSanford, @jgong15, @GIMedOnc, @ronanhsieh

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FDA withdraws the accelerated approval of adagrasib plus cetuximab in KRAS G12C colorectal cancer after KRYSTAL-10 misses both primary endpoints

The accelerated approval of adagrasib plus cetuximab in metastatic colorectal cancer was officially withdrawn September 1 after KRYSTAL-10 failed to confirm benefit. The phase 3 trial randomized 461 patients in the second-line setting to adagrasib plus cetuximab versus chemotherapy with or without VEGF inhibition, and missed both primary endpoints: PFS 7.5 versus 8.1 months (HR 0.89) and OS 21.6 versus 21.7 months (HR 0.83). The response rate of 47% versus 16% nonetheless leaves open the question of whether the combination retains a niche for patients who need depth of response to enable curative-intent surgery, and adagrasib in metastatic colon cancer now appears on lists of oncology drugs withdrawn or soon to be withdrawn from the market.

Discussed by: @GIMedOnc, @OncBrothers

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HERIZON-GEA-01 second interim analysis: zanidatamab plus chemotherapy improves overall survival versus trastuzumab plus chemotherapy in first-line HER2-positive gastroesophageal adenocarcinoma

The second interim analysis of HERIZON-GEA-01 showed that zanidatamab plus chemotherapy significantly improved overall survival versus trastuzumab plus chemotherapy as first-line treatment for HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma — notably, without a PD-1 antibody in the regimen. At the first interim analysis the OS hazard ratio had been 0.80 with P=0.06; no updated HR figures were released with the second interim read-out. Separately, zanidatamab plus chemotherapy with or without tislelizumab had received FDA approval in first-line metastatic HER2-positive gastroesophageal adenocarcinoma on the basis of a median OS of 26.4 versus 19.2 months, leaving clinicians to weigh whether a checkpoint inhibitor remains necessary alongside a regimen that appears to improve OS on its own.

Discussed by: @OncoAlert, @MorningGlorySci, @OncBrothers, @CancerNetwrk

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GlutaPanc phase 1 in Nature Cancer: adding FDA-approved high-dose L-glutamine to gemcitabine plus nab-paclitaxel in first-line metastatic pancreatic cancer

The phase 1 GlutaPanc trial, described as the first formal translation of an FDA-approved L-glutamine formulation as a chemosensitizer in first-line metastatic pancreatic cancer, paired high-dose L-glutamine with gemcitabine and nab-paclitaxel in 16 treatment-naive patients. The combination reached its recommended phase 2 dose; tumor shrinkage occurred in 94% of participants, with a 44% overall response rate including 12.5% complete responses, median PFS of 8.5 months, and median OS of 22 months. Proposed mechanisms include effects on intermediary metabolism, gut bacterial metabolism, inflammatory response, and anti-cachexia effects, and colleagues noted the trial included extensive metabolomic and metagenomic correlatives alongside the efficacy signal.

Discussed by: @jgong15, @AnthonyNguyenMD, @jgong15, @OncoAlert

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Gastrectomy after systemic therapy in cStage IVB gastric cancer: 3-year OS 65% in 121 selected patients

In 121 selected patients undergoing gastrectomy after systemic therapy for cStage IVB gastric cancer, 3-year OS was 65%, with outcomes of 76% in oligometastatic disease versus 43% in non-oligometastatic disease, and major pathologic response associated with 3-year OS of 89–97%. The data prompted discussion around whether response and metastatic burden may matter more than technical resectability alone when selecting patients for conversion surgery. Separately, the broader context of stage IV gastric cancer management included debate over whether immune checkpoint blockade in dMMR/MSI-H gastric cancer rests on solid evidence or constitutes premature extrapolation.

Discussed by: @ronanhsieh, @JCO_ASCO

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🔥 Top Ranked Tweets

Neeraj Agarwal, MD, FASCO @neerajaiims

RT @OncoAlert: This week's OncoAlert 🚨 Newsletter is packed with practice-changing data:
REGISTER TO GET IT 👉 https://t.co/NhtuRoIyO3

NOW OUT!
✅️ FDA 🇺🇸 approves daraxonrasib — first-in-class RAS inhibitor for metastatic #PancreaticCancer
✅️FDA approves zanidatamab-hrii + tislelizumab-jsgr for HER2+ gastric/GEJ/esophageal cancer
✅️Merck & Moderna's INTerpath-001 hits its endpoints — mRNA neoantigen therapy + pembrolizumab in resected #melanoma
✅️5-year KEYNOTE-671 data confirms durable benefit of perioperative pembrolizumab in resectable NSCLC #LungCancer
✅️Dose-escalated radiotherapy (80 Gy) improves 10-year PFS in high-risk #ProstateCancer (GETUG AFU 18)

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