The ESDO BULLETS by the Young Group of the European Society of Digestive Oncology provide regular overviews and summaries of the latest publications in GI oncology from major journals. We cover topics which are interesting for digestive oncology specialists as well as for clinicians with multi-disciplinary background.

The bullets provide direct links to each publication. We hope you find this summary of the latest developments in digestive cancers of benefit to you in your practice and kindly ask you to share our content with your circles.

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bullets April 2023


In Chinese single-arm phase II trial, definitive chemoradiotherapy (50,4 Gy with 5 weekly cycles of cisplatin + paclitaxel) combined with toripalimab (anti PD-1, concurrent with CRTx and continued up to 1 y) demonstrated encouraging activity in locally advanced unresectable ESCC (1-y OS: 78.4%, 1-y PFS: 54.5%).

Zhu Y, et al. Lancet Oncol., Volume 24, Issue 4, 371 – 382



  • Zolbetuximab plus mFOLFOX6 improves survival in patients with CLDN18.2-positive, HER2-negative unresectable/metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT)

In randomized phase III trial, the addition of zolbetuximab (anti-CLDN18.2 antibody) to 1L mFOLFOX6 chemotherapy improved PFS and OS in patients with CLDN18.2-positive, HER2-negative unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma – mPFS: 10.61 vs 8.67 mo,  HR = 0.75, 95% CI 0.60–0.94; p=.0066; mOS: 18.23 vs 15.54 mo, HR = 0.75, 95% CI 0.60–0.94; p=.0053.

Shita K, et al. Lancet (2023)



In retrospective analysis of phase II PanaMa trial, consensus molecular subtypes (CMS) influenced outcomes (ORR, PFS, OS) in patients with RAS wild-type mCRC treated with 5-FU and folinic acid with or without panitumumab after mFOLFOX6 + panitumumab induction. More favorable outcomes were observed for CMS2 (canonical) and CMS4 (mesenchymal) subtypes, while CMS1 (MSI immune) and CMS3 (metabolic) subtypes were associated with less favorable PFS and OS. The addition of panitumumab to the maintenance chemotherapy improved PFS in CMS2 and OS in CMS4, but produced no benefits in CMS1/3.

Stahler A, et al. J Clin Oncol. (2023)

  • Neoadjuvant pembrolizumab in localized microsatellite instability high/deficient mismatch repair solid tumors

 In a single-arm phase II trial, neoadjuvant pembrolizumab was administered to dMMR/MSI-H cancer patients (27 with CRC and 8 with non-colorectal cancers) up to 6 months before surgery, with an option to continue for 12 months after surgery. The trial produced high rates of ORR (82%) and pathological CR (65% in resected cases). 17 patients were managed without surgery, with 2 cases of PD.

Ludford K, et al. J Clin Oncol. 2023 41:12, 2181-2190



  • Adjuvant nab-paclitaxel + gemcitabine does not improve disease-free survival as compared to gemcitabine alone in pancreatic adenocarcinoma (APACT phase III trial)

 In resected pancreatic ductal adenocarcinoma adjuvant nab-paclitaxel + gemcitabine did not improve independently assessed disease-free survival (iDFS) as compared to gemcitabine alone (the primary end-point – median iDFS: 19.4 vs 18.8 mo, HR = 0.88; 95% CI, 0.729 to 1.063; P = .18). Mature OS favored nab-paclitaxel + gemcitabine versus gemcitabine (mOS: 41.8 vs 37.7 mo; HR = 0.80; 95% CI, 0.678 to 0.947; P = .0091).

Tempero MA, et al. J Clin Oncol. 2023 41:11, 2007-2019



In randomized Chinese phase III trial, the use of adjuvant Hepatic Arterial Infusion Chemotherapy (HAIC; 1 or 2 cycles of FOLFOX) improved disease-free survival after radical resection of HCC with microvascular invasion) – median DFS: 20.3 mo for HAIC vs 10.0 mo for routine follow-up; HR = 0.59; 95% CI, 0.43 to 0.81; P = .001). No significant difference in OS was detected.

Li S-H et al. J Clin Oncol. 2023 41:10, 1898-1908



In randomized phase III, the addition of pembrolizumab to 1L chemotherapy (cisplatin for up to 8 cycles and gemcitabine with no maximum duration) modestly improved OS in patients with advanced biliary tract cancer (mOS: 12.7 mo vs 10.9 mo, HR = 0.83; 95% CI 0.72–0.95; P = .0034). No significant differences in ORR or PFS were observed.

Kelly RK, et. al. Lancet 2023 (online)



bullets March 2023


  • 1st line pembrolizumab + chemotherapy in advanced gastric/esophagogastric junction adenocarcinoma (KEYNOTE-859)

Pembrolizumab added to fluoropyrimidine- and platinum-containing chemotherapy (PF or CAPOX) improved ORR, PFS and OS in patients with advanced HER2-negative gastric/esophagogastric junction adenocarcinoma (mOS: 12.9 mo with pembro + chemo vs 11.5 mo with placebo + chemo, HR = 0.78, 95% CI 0.70-0.87; P < 0.0001). Results were consistent across PD-L1 expression subgroups.

Rha SY, et al. Annals of Oncology, Volume 34, Issue 3, 319 - 320


  • PD-1 antibody plus chemotherapy in patients with advanced ESCC with low PD-L1 expression.

Meta-analysis of randomized phase III trials indicated superiority of PD-1 antibody plus chemotherapy to chemotherapy alone in terms of OS and ORR in patients with advanced esophageal squamous cell carcinoma with low PD-L1 expression.

Wu XH, et al. J Clin Oncol. 2023 41:9, 1735-1746



  • Germline mutations in homologous-recombination genes influence the risk of gastric cancer in patients infected with H. pylori

Results of a large Japanese study indicate that germline pathogenic variants in homologous recombination genes (BRCA1, BRCA2, PALB2, ATM) significantly increase the risk of gastric cancer, but only in carriers that were infected with Helicobacter pylori.

Usui Y, et al. N Engl J Med 2023; 388:1181-1190



  • Patients with KRAS G12-mutant mCRC do not derive benefit from treatment with trifluridine/tipiracil.

In large retrospective analysis of real world data and results of phase III RECOURSE trial, OS was not prolonged with treatment with trifluridine/tipiracil versus placebo in patients with KRAS G12-mutant metastatic colorectal cancers (HR = 0.97; 95% CI 0.73–1.20; P = 0.85). In contrast, FTD/TPI was highly effective in KRAS G13-mutant CRC. The predictive influence of KRAS mutational status was confirmed in vitro.

Van de Haar J, et. al. Nature Medicine, volume 29, 605–614 (2023).


  • Preoperative Chemotherapy improves outcomes in operable Colon Cancer (FOxTROT).

In FOxTROT randomized phase III trial 6 weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy for operable colon cancer (cT3-4, N0-2, M0) produced histopathologic down-staging, improved resectability, and reduced the 2-year recurrence rate (16.9% preoperative chemotherapy vs 21.5% control; HR = 0.72 [95% CI, 0.54 to 0.98]; P = .037). Preoperative panitumumab did not enhance the benefit. The advantage of preoperative chemotherapy was not seen in dMMR cancers.

Morton D, et al. J Clin Oncol. 2023 41:8, 1541-1552



In randomized, phase II trial comparing temozolomide versus capecitabine/temozolomide in patients with advanced pancreatic NETs (G1-G2), capecitabine + temozolomide significantly improved progression-free survival. No change in OS was detected.

Kunz PL, et al. J Clin Oncol. 2023 41:7, 1359-1369


  • 2nd line FOLFIRI + bevacizumab vs FOLFIRI in advanced NEC (PRODIGE 41-BEVANEC)

In phase 2 randomized trial the addition of bevacizumab to FOLFIRI in 2nd line treatment of advanced neuroendocrine carcinomas (gastroenteropancreatic or of unknown primary origin) did not improve 6-month overall survival.

Walter D, et al. Lancet Oncol. 2023 Mar;24(3):297-306



  • 2nd line pembrolizumab in Asian patients with advanced HCC (KEYNOTE-394)

In randomized, phase III trial treatment with pembrolizumab improves ORR, PFS and OS vs placebo in Asian patients with advanced hepatocellular carcinoma who progressed or did not tolerate sorafenib.

Qin S, et al. J Clin Oncol. 2023 41:7, 1434-1443




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