ASCO 2026 GI Cancer Highlights: Beyond the LBAs

The 2026 ASCO Annual Meeting delivered a robust gastrointestinal cancers program extending well beyond its late-breaking abstracts. The following highlights capture key findings from across the meeting in pancreatic cancer, cholangiocarcinoma, hepatocellular carcinoma, gastroesophageal adenocarcinoma, and colorectal cancer.

Novel MEK Inhibitor Atebimetinib Shows Promise in First-Line Pancreatic Cancer

The pulsatile MEK1/2 inhibitor atebimetinib demonstrated encouraging efficacy and a favorable tolerability profile when combined with modified gemcitabine and nab-paclitaxel (Abraxane; mGnP) in patients with first-line metastatic pancreatic ductal adenocarcinoma (PDAC), according to phase 2a results.¹

Among 50 response-evaluable patients, the confirmed ORR was 36% (95% CI, 23%-51%) and DCR was 82% (95% CI, 69%-91%). Across the full expanded cohort (n = 55), median OS was 17.3 months (95% CI, 11.2-not reached) and median PFS was 8.3 months (95% CI, 5.9-9.6). Activity was consistent across RAS mutation subtypes, with an ORR of 40% and DCR of 86% in ctDNA-detected RAS-mutant patients (n = 43). Notably, 84% of patients were weight stable or gained weight at 3 months.

Grade ≥3 TRAEs were predominantly hematologic and attributed to the chemotherapy backbone. Only 1 patient discontinued atebimetinib, and no discontinuations were toxicity-related. MEK inhibitor class toxicities were largely absent at higher grades.

"The combination showed promising efficacy across ORR, DCR, PFS, and OS," said lead author Peter Vu, MD, MHA, of UC San Diego Moores Cancer Center. The global phase 3 MAPKeeper 301 trial comparing atebimetinib plus mGnP versus standard gemcitabine and nab-paclitaxel is now recruiting.

First-Line Pemigatinib Improves PFS in FGFR2-Rearranged Cholangiocarcinoma

First-line pemigatinib (Pemazyre) significantly reduced the risk of progression or death compared with gemcitabine plus cisplatin in patients with unresectable advanced or metastatic cholangiocarcinoma harboring FGFR2 rearrangements, according to phase 3 FIGHT-302 trial results.²

Pemigatinib (n = 83) produced a median progression-free survival (PFS) of 8.34 months (95% CI, 6.51-12.22) versus 6.80 months (95% CI, 6.05-8.25) with gemcitabine plus cisplatin (n = 84; HR, 0.584; 95% CI, 0.393-0.868; P = .0078). The objective response rate (ORR) was 47.0% with pemigatinib versus 15.5% with chemotherapy (odds ratio [OR], 5.57; P < .0001), and the disease control rate (DCR) was 89.2% versus 67.9% (OR, 4.10; P = .0007).

Median duration of response was 14.2 months versus 6.3 months. Overall survival (OS) was not significantly different between arms (median 24.4 vs 25.0 months; HR, 1.095; P = .6581), though approximately 80% of chemotherapy-arm patients crossed over to FGFR inhibitor therapy after progression. An exploratory ctDNA analysis identified emergent secondary FGFR2 mutations at progression in approximately one-third of pemigatinib-treated patients.

Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 78.3% of pemigatinib patients versus 67.1% with chemotherapy. The most common TEAEs with pemigatinib included hyperphosphatemia (81.9%), alopecia (56.6%), and palmar-plantar erythrodysesthesia syndrome (47.0%).

"Results support potential consideration of pemigatinib in the first-line setting for patients with FGFR2-rearranged cholangiocarcinoma," said lead author Tanios S. Bekaii-Saab, MD, of Mayo Clinic.

Camrelizumab Plus Rivoceranib and TACE Improves PFS in Unresectable HCC

Adding camrelizumab and rivoceranib to transarterial chemoembolization (TACE) significantly improved PFS over TACE alone in patients with unresectable hepatocellular carcinoma (HCC) eligible for embolization, according to a phase 3 trial.³

The median PFS by blinded independent review committee (BIRC) per modified RECIST was 11.1 months (95% CI, 7.8-14.0) with camrelizumab plus rivoceranib and TACE versus 8.3 months (95% CI, 6.9-9.5) with TACE alone (HR, 0.73; 95% CI, 0.56-0.96; P = .0127). The ORR was 60.3% versus 45.5%, and the median duration of response (DOR) was 16.6 versus 8.2 months. OS data were immature, though a favorable trend was observed (HR, 0.76; 95% CI, 0.46-1.24), with 24-month OS rates of 82.0% versus 73.3%.

Grade ≥3 treatment-related adverse events (TRAEs) occurred in 73.7% of investigational arm patients versus 28.7% with TACE alone, and serious TRAEs in 31.0% versus 4.3%. TRAEs led to discontinuation in 22.1% of patients in the combination arm.

"Camrelizumab plus rivoceranib with TACE provided a statistically significant and clinically meaningful improvement in PFS vs TACE, with manageable safety," said presenting author Tao Peng, MD, of The First Affiliated Hospital of Guangxi Medical University.

Zanidatamab Triplet Benefit Independent of PD-L1 Status in HER2-Positive Gastroesophageal Adenocarcinoma

A preplanned PD-L1 subgroup analysis from the phase 3 HERIZON-GEA-01 trial shows that zanidatamab-hrii (Ziihera) plus tislelizumab (Tevimbra) and chemotherapy improves PFS and OS versus trastuzumab (Herceptin) plus chemotherapy in frontline HER2-positive gastroesophageal adenocarcinoma (GEA), regardless of PD-L1 expression.⁴

In the overall population, the median PFS was 12.4 months with the zanidatamab triplet (n = 302) versus 8.1 months with trastuzumab plus chemotherapy (n = 308; HR, 0.63; P < .0001), and median OS was 26.4 versus 19.2 months (HR, 0.72; P = .0043). PFS and OS benefits were consistent across both PD-L1–positive and PD-L1–negative subgroups whether assessed by tumor area positivity (TAP) score or combined positive score (CPS). Notably, OS benefit appeared numerically greater in PD-L1-negative patients, with HRs of 0.49 (TAP < 1%) and 0.43 (CPS < 1).

Grade ≥3 TRAEs occurred in 71.8% of zanidatamab triplet patients versus 59.6% with trastuzumab plus chemotherapy. Noninfectious pulmonary toxicities and left ventricular dysfunction were more frequent in the zanidatamab arm.

"These benefits were consistent in patients with PD-L1–positive and PD–negative disease," said presenting author Sun Young Rha, MD, PhD, of Yonsei Cancer Center.

ctDNA Dynamics During Adjuvant Chemotherapy Stratify Recurrence Risk in Colorectal Cancer

Circulating tumor DNA (ctDNA) dynamics measured at approximately 3 months of adjuvant chemotherapy (ACT) provide clinically meaningful stratification of recurrence risk and may inform treatment duration decisions in resected colorectal cancer (CRC), according to a retrospective analysis of the CIRCULATE-Japan GALAXY study.⁵

Among 1028 analyzed patients, those with rising ctDNA had markedly worse disease-free survival (DFS) outcomes versus the sustained-negative reference group (HR, 124.38; 95% CI, 67.99-227.55; P < .001; median DFS, 1.1 months). Patients with decreasing but detectable ctDNA had an HR of 13.15 (P < .001; median DFS, 5.3 months), while those achieving clearance had an HR of 3.87 (P < .001). In the sustained-negative and ctDNA clearance groups, longer ACT conferred no additional DFS benefit. However, among patients with partial molecular response (decreasing but detectable), longer ACT was associated with improved DFS (median 5.9 vs 1.7 months; HR, 3.64; 95% CI, 1.33-9.97; P = .008).

The analysis was retrospective with inherent limitations including variability in ctDNA testing timing and ACT duration. Prospective validation is required before clinical implementation.

"ctDNA dynamics after 3 months of ACT provide clinically meaningful stratification of recurrence risk," said presenting author Eiji Oki, MD, PhD, of Kyushu University Hospital.

References

1. Vu P, Chung V, Hosein PJ, et al. Results from a phase 2a study of atebimetinib in combination with mGnP in advanced or metastatic pancreatic cancer. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 4013.

2. Bekaii-Saab TS, Melisi D, Wilmink H, et al. Pemigatinib for unresectable advanced or metastatic cholangiocarcinoma with FGFR2 rearrangement: results from the confirmatory phase 3 FIGHT-302 trial. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 4017.

3. Jia W, Qin S, Zhou J, et al. Camrelizumab (C) plus rivoceranib (R) with transarterial chemoembolization (TACE) vs TACE alone in unresectable hepatocellular carcinoma (uHCC): a randomized, phase 3 trial. J Clin Oncol. 2026;44(suppl 16):4001. doi:10.1200/JCO.2026.44.16_suppl.4001

4. Rha SY, Shitara K, Lin S, et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma (mGEA): PD-L1 subgroup analysis from HERIZON-GEA-01. J Clin Oncol. 2026;44(suppl 16):4010. doi:10.1200/JCO.2026.44.16_suppl.4010

5. Oki E, Yamamoto H, Bando H, et al. Informing optimal duration of adjuvant chemotherapy (ACT) in resected stage I-IV colorectal cancer (CRC) based on early circulating tumor DNA (ctDNA) dynamics. J Clin Oncol. 2026;44(suppl 16):3501.