Revisit the Top Presentations and Biggest Data From the 2025 Gastrointestinal Cancers Symposium

The 2025 Gastrointestinal Cancers Symposium wrapped up on Saturday following 3 days of impactful presentations highlighting emerging data from across the field.

In case you missed them in San Francisco, here are some of the top abstracts presented at this year’s meeting. Check out full coverage of the meeting here.

Frontline Nivolumab/Ipilimumab Improves OS in Unresectable HCC

Treatment with the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) led to a statistically significant and clinically meaningful improvement in overall survival (OS) vs lenvatinib (Lenvima) or sorafenib (Nexavar) in patients with previously untreated unresectable hepatocellular carcinoma (HCC), according to data from the phase 3 CheckMate 9DW study (NCT04039607).¹

The median OS was 23.7 months for patients treated with nivolumab plus ipilimumab vs 20.6 months for those given lenvatinib or sorafenib (HR, 0.79; 95% CI, 0.65-0.96; P = .018).

Nivolumab Plus Ipilimumab Prolongs PFS vs Nivolumab Alone in MSI-H/dMMR mCRC

The combination of nivolumab and ipilimumab produced an improvement in progression-free survival (PFS) vs nivolumab alone across all lines of therapy in patients with mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC), according to data from the phase 3 CheckMate 8HW trial (NCT04008030).²

The median PFS was not reached (95% CI, 53.8 months-not evaluable [NE]) for nivolumab plus ipilimumab vs 39.3 months (95% CI, 22.1-NE) for nivolumab monotherapy (HR, 0.62; 95% CI, 0.48-0.81; P = .0003).

Encorafenib/Cetuximab Plus Chemo Drives ORR Improvement in BRAF V600E+ mCRC

The addition of encorafenib (Braftovi) and cetuximab (Erbitux) to standard-of-care mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) generated a statistically significant and clinically meaningful improvement in overall response rate (ORR) compared with mFOLFOX6 alone in patients with BRAF V600E–mutated mCRC, according to data from the phase 3 BREAKWATER trial (NCT04607421).³

The ORR was 60.9% (95% CI, 51.6%-69.5%) with the combination (n = 110) vs 40.0% (95% CI, 31.3%-49.3%) for mFOLFOX6 alone (n = 110; odds ratio, 2.443; 95% CI, 1.403-4.253; one-sided P = .0008). These data supported the December 2024 FDA accelerated approval of encorafenib in combination with cetuximab and mFOLFOX6 for the treatment of patients with mCRC harboring a BRAF V600E mutation, as detected by an FDA-approved test.

Dose Reductions of Liposomal Irinotecan, Oxaliplatin Are Not Associated With Worsened OS in Metastatic PDAC

Dose reductions of liposomal irinotecan (Onivyde) and oxaliplatin did not negatively affect OS outcomes in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) treated with NALIRIFOX (liposomal irinotecan, oxaliplatin, 5-fluorouracil, and leucovorin) during the phase 3 NAPOLI 3 trial (NCT04083235), according to exploratory post hoc findings from the study.⁴

Patients who required dose reductions of liposomal irinotecan experienced a median OS of 12.6 months (95% CI, 11.0-14.5) vs 9.4 months (95% CI, 7.5-11.5) for those without a dose reduction. Similarly, patients receiving dose reductions of oxaliplatin achieved a median OS of 13.5 months (95% CI, 11.7-15.2) vs 7.7 months (95% CI, 6.2-10.2) in patients who did not receive a dose reduction of the agent.

Aspirin Is Associated With Reduced Recurrence Risk in PI3K+ CRC

Three-year treatment with aspirin was associated with a reduction in the risk of recurrence compared with placebo in patients with PIK3CA-mutated CRC, according to data from the phase 3 ALASCCA trial (NCT02647099).⁵

The risk of disease recurrence was reduced by 51% in patients with PIK3CA exon 9/20 mutations (HR, 0.49; 95% CI, 0.24-0.98; P = .044) and by 58% in patients with PIK3R1, PTEN, or other PIK3CA alterations (HR, 0.42; 95% CI, 0.21-0.83; P = .013).

Cabozantinib Bests Placebo in Extrapancreatic NETs With Primary Tumor Arising in the Gl Tract

Cabozantinib (Cabometyx) generated an improvement in PFS vs placebo in patients with extrapancreatic neuroendocrine tumors (NETs) with a primary tumor arising in the gastrointestinal tract whose disease progressed on prior therapy, according to subgroup data from the phase 3 CABINET trial (NCT03375320).⁶

In the cohort of patients with extrapancreatic NETs with a primary tumor arising in the gastrointestinal tract, the median PFS was 8.5 months (95% CI, 6.0-16.7) for cabozantinib compared with 5.6 months (95% CI, 3.9-11.0) for placebo (stratified HR, 0.50; 95% CI, 0.28-0.88; 1-sided stratified log-rank P = .007).

NIPS Boosts OS Over PS in Gastric Cancer With Peritoneal Metastasis

Treatment with intraperitoneal and intravenous paclitaxel plus S-1 (NIPS) boosted OS compared with intravenous paclitaxel and S-1 alone (PS) in patients with gastric cancer and peritoneal metastasis, according to data from the phase 3 DRAGON-01 trial (ChiCTR-IIR-16009802).⁷

NIPS generated a median OS of 19.4 months (95% CI, 17.1-22.9) vs 13.9 months (95% CI, 10.3-16.1) for PS (HR, 0.66; 95% CI, 0.49-0.88; P = .0056).

Pelareorep Plus mFOLFIRINOX ± Atezolizumab Shows Acceptable Safety in Metastatic PDAC

The addition of Pelareorep to mFOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and fluorouracil) with or without atezolizumab (Tecentriq) demonstrated safety with no new signals in patients with newly diagnosed metastatic PDAC, according to findings from cohort 5 of the safety run-in portion of the ongoing phase 1/2 GOBLET study (Eudra-CT:2020-003996-16).⁸

ctDNA Status Is Prognostic for DFS With Celecoxib in Stage III Resected Colon Cancer

A positive circulating tumor DNA (ctDNA) status was strongly associated with worse disease-free survival (DFS) outcomes vs negative ctDNA status in patients with stage III resected colon cancer, according to findings from a subgroup analysis of the phase 3 CALGB (Alliance)/SWOG 80702 trial (NCT01150045).⁹

Notably, DFS outcomes were significantly improved with celecoxib (Celebrex) vs placebo in patients with ctDNA-positive disease.

Addition of Camrelizumab and Rivoceranib to TACE Boosts PFS in Unresectable HCC

Treatment with the combination of camrelizumab, rivoceranib, and transarterial chemoembolization (TACE) led to a statistically significant improvement in PFS vs TACE alone in patients with unresectable HCC, according to findings from the phase 2 CARES-005 trial (NCT04559607).¹⁰

Patients treated with the combination achieved a median PFS of 10.8 months (95% CI, 8.8-13.7) vs 3.2 months (95% CI, 2.4-4.2) for those given TACE alone (HR, 0.34; 95% CI, 0.24-0.50; P < .0001).

Trifluridine/Tipiracil Demonstrates DFS Benefit Over Placebo in Resected Stage IV CRC

A subset of patients with stage IV CRC experienced a clinically meaningful improvement in DFS when treated with trifluridine/tipiracil (TAS-102; Lonsurf) vs placebo; however, TAS-102 did not generate a statistically significant improvement in DFS in the full population of patients, according to data from the phase 3 ALTAIR study (NCT04457297).¹¹

In all patients, the median DFS 9.30 months (7.92-10.84) for TAS-102 vs 5.55 months (4.17-7.33) for placebo (HR, 0.79; 95% CI, 0.60-1.05; P = .107). In the subset of patients with stage IV disease, the median DFS was 9.76 months (95% CI, 7.62-11.76) and 3.96 months (95% CI, 3.71-7.98), respectively (HR, 0.53; 95% CI, 0.32-0.87; P = .012).

References

1. Kudo M, Yau T, Decaens T, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) therapy for unresectable hepatocellular carcinoma (uHCC): CheckMate 9DW expanded analyses. J Clin Oncol. 2025;43(suppl 4):520. doi:10.1200/JCO.2025.43.4_suppl.520
2. Andre T, Elez E, Lenz H-J, et al. First results of nivolumab (NIVO) plus ipilimumab (IPI) vs NIVO monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) from CheckMate 8HW. J Clin Oncol. 2025;43(suppl 4):LBA143. doi:10.1200/JCO.2025.43.4_suppl.LBA143
3. Kopetz S, Yoshino T, Van Cutsem E, et al. BREAKWATER: Analysis of first-line encorafenib + cetuximab + chemotherapy in BRAF V600E-mutant metastatic colorectal cancer. J Clin Oncol. 2025;43(supp 4):16. doi:10.1200/JCO.2025.43.4_suppl.16
4. Patel A, Laursen A, Cockrum P, et al. Effect of dose adjustments on overall survival in patients with metastatic pancreatic ductal adenocarcinoma treated with NALIRIFOX: a post hoc analysis of NAPOLI 3. J Clin Oncol. 2025;43(suppl 4);716. doi:10.1200/JCO.2025.43.4_suppl.716
5. Martling A, Lindberg J, Myrberg IH, et al. Low-dose aspirin to reduce recurrence rate in colorectal cancer patients with PI3K pathway alterations: 3-year results from a randomized placebo-controlled trial. J Clin Oncol. 2025;43(4):LBA125.
6. Strosberg J, Zemla T, Geyer S, et al. Efficacy and safety of cabozantinib for advanced gastrointestinal (GI) neuroendocrine tumors (NET) after progression on prior therapy: subgroup analysis of the phase 3 CABINET trial (Alliance A021602). J Clin Oncol. 2025;43(suppl 4):666. doi:10.1200/JCO.2025.43.4_suppl.666
7. Yan C, Yang Z, Shi Z, et al. Intraperitoneal and intravenous paclitaxel plus S-1 versus intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis: Results from the multicenter, randomized, phase 3 DRAGON-01 trial. J Clin Oncol. 2025;43(suppl 4):327. doi:10.1200/JCO.2025.43.4_suppl.327
8. Seufferlein T, Arnold D, Burkhart N, et al. GOBLET study: Results of the safety run-in for first-line metastatic pancreatic ductal adenocarcinoma (PDAC) patients treated with pelareorep + modified FOLFIRINOX +/- atezolizumab. J Clin Oncol. 2025;43(suppl 4):730. doi:10.1200/JCO.2025.43.4_suppl.730
9. Nowak JA, Shi Q, Twombly T, et al. Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: findings from CALGB (Alliance)/SWOG 80702. J Clin Oncol. 2025;43(supp 4):LBA14. doi:10.1200/JCO.2025.43.4_suppl.LBA14
10. Zhu H, Teng G-J, Fan W, et al. Transarterial chemoembolization (TACE) combined with camrelizumab and apatinib versus TACE alone in the treatment of unresectable hepatocellular carcinoma eligible for embolization: A multicenter, open-label, randomized, phase 2 study (CAP-ACE). J Clin Oncol. 2025;43(suppl 4):LBA522. doi:10.1200/JCO.2025.43.4_suppl.LBA522
11. Bando H, Watanabe J, Kotaka M, et al. A randomized, double-blind, phase III study comparing trifluridine/tipiracil (FTD/TPI) versus placebo in patients with molecular residual disease following curative resection of colorectal cancer (CRC): the ALTAIR study. J Clin Oncol. 2025;43(suppl 4):LBA22. doi:10.1200/JCO.2025.43.4_suppl.LBA22