Gastrointestinal oncology at ASCO 2026: Six key late-breakers

Colorectal cancer

CIRCULATE: ctDNA-guided adjuvant therapy in stage II colon cancer

→ LBA3500: Folprecht G, Stasik S, Christmann J, et al. Disease-free survival (DFS) and time to recurrence (TTR) with circulating tumor (ct) DNA–based decision for adjuvant treatment in colon cancer stage II (CIRCULATE): An AIO (KRK-0217)/ABCSG trial. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026

The phase III CIRCULATE trial (NCT04089631) evaluated whether postoperative Circulating tumor DNA can guide adjuvant chemotherapy decisions in stage II pMMR/MSS colon cancer. Among 2,126 screened patients, the ctDNA-positive rate was lower than anticipated at 2.9% in randomized patients. Overall, 1,396 patients were randomized: 1,083 to OFF-STUDY, 287 to OBS (15 ctDNApos), and 26 pts to CHEMO (all ctDNApos).

From 06/2020 to 07/2025, 2,126 pts were screened at 138 sites in Germany/Austria. At three years, disease-free survival (DFS) and overall survival (OS) were significantly higher in ctDNA-negative versus ctDNA-positive patients (3-year DFS 87% vs 52%; HR 0.23, p<0.001; 3-year OS 98% vs 88%; HR 0.18, p=0.001). In the per-protocol analysis, chemotherapy improved 3-year recurrence rates (19% vs 62%; HR 0.21, p=0.009) and DFS (77% vs 38%; HR 0.28, p=0.022) compared with observation. However, these differences were not statistically significant in the intention-to-treat analysis.

In the endpoint analysis, relapse-free survival (RFS) numerically favored avelumab over placebo, with a stratified hazard ratio (HR) for failure of 0.61 (95% CI 0.32–1.16; p=0.132) and an adjusted stratified HR of 0.54 (95% CI 0.28–1.05; p=0.069). RFS events occurred in 16 versus 24 patients, respectively. For MCC relapse, the stratified HR was 0.51 (95% CI 0.26–1.00), and the adjusted stratified HR was 0.47 (95% CI 0.23–0.94), with 13 versus 23 events in the avelumab and placebo arms. For distant metastasis-free survival (DMFS), the stratified HR was 0.93 (95% CI 0.44–1.97), with 13 versus 15 events. The HRs for disease-specific survival (DSS) and overall survival (OS) were 1.81 (95% CI 0.43–7.55; 5 versus 3 events) and 2.37 (95% CI 0.73–7.73; 9 versus 5 events), respectively.

Key clinical takeaway

This study provides prospective randomized evidence supporting ctDNA as a tool for adjuvant decision-making in stage II colon cancer. However, interpretation is limited by the small ctDNA-positive cohort and reliance on per-protocol analyses. The findings strengthen the case for ctDNA-guided risk stratification, but broader validation remains necessary before universal implementation.

BREAKWATER Cohort 3: Encorafenib plus cetuximab and FOLFIRI in BRAF V600E-mutant mCRC

→ LBA3503: Kopetz S, Tabernero J, Lonardi S, et al. BREAKWATER: Progression-free and overall survival analyses of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC). Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026

The BREAKWATER Cohort 3 study (NCT04607421) examined first-line Encorafenib plus Cetuximab with FOLFIRI in untreated BRAF V600E-mutant metastatic colorectal cancer. A total of 147 patients were randomized. Previously, the cohort met its primary endpoint with confirmed ORR of 64.4% versus 39.2% for control (odds ratio 2.76; p=0.001). Updated data presented at ASCO 2026 showed that the regimen also met the key secondary endpoint of progression-free survival (PFS), with prolonged OS also observed. Median treatment duration was 67.9 weeks versus 32.1 weeks in the control arm. Treatment discontinuation due to adverse events was similar between arms (14% vs 10%).

Key clinical takeaway

These results extend the BREAKWATER data set and support greater flexibility in chemotherapy backbone selection for BRAF V600E-mutant metastatic colorectal cancer. Together with earlier mFOLFOX6 data, the findings reinforce earlier incorporation of targeted therapy in this subgroup.

Hepatocellular carcinoma 

EMERALD-3: STRIDE ± lenvatinib plus TACE in unresectable HCC

→ LBA4000: Abou-Alfa GK, Ren Z, Erinjeri JP, et al. Efficacy and safety results from EMERALD-3: A phase 3, randomized study of tremelimumab plus durvalumab with or without lenvatinib combined with transarterial chemoembolization (TACE) in participants (pts) with unresectable embolization-eligible hepatocellular carcinoma (eeHCC). Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026

The phase III EMERALD-3 study (NCT05301842) evaluated the addition of Tremelimumab plus Durvalumab (STRIDE), with or without Lenvatinib, to transarterial chemoembolization (TACE) in embolization-eligible Hepatocellular carcinoma. A total of 293 patients received STRIDE plus lenvatinib plus TACE, 175 STRIDE plus TACE, and 292 TACE alone. STRIDE plus lenvatinib plus TACE improved PFS versus TACE (HR 0.70; p=0.0007), while OS showed a non-significant trend (HR 0.84; p=0.1814). STRIDE plus TACE also improved both PFS (HR 0.71) and OS (HR 0.70). Grade 3/4 treatment-related adverse events occurred in 62.7%, 48.6%, and 18.6% of patients, respectively.

Key clinical takeaway

These findings suggest that integrating immunotherapy into locoregional treatment may improve outcomes in intermediate-stage HCC. Notably, STRIDE plus TACE alone showed an OS signal, which may be clinically relevant given the lower toxicity compared with the triplet approach.

Gastric cancer 

Neo-CRAG: Neoadjuvant chemoradiotherapy in locally advanced gastric cancer

→ LBA4075: Xu RH, Wang W, Zhang YJ, et al. Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by D2 gastrectomy and adjuvant chemotherapy for locally advanced gastric cancer (Neo-CRAG): A randomized, multicenter, phase 3 trial. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026

The Neo-CRAG phase III trial (NCT01815853) compared neoadjuvant chemoradiotherapy (CRT) versus chemotherapy alone before D2 gastrectomy in locally advanced Gastric cancer. Among 620 patients, median follow-up was 69.7 months. The primary endpoint of DFS was met (HR 0.750; p=0.008). Three-year DFS was 55.6% with CRT versus 42.4% with chemotherapy, with median DFS of 52.7 versus 24.4 months. Five-year OS was 50.1% versus 44.2% (HR 0.781; p=0.025). Pathologic complete response rates were 14.8% versus 6.2%, and locoregional recurrence after R0 resection was lower with CRT (9.4% vs 18.3%).

Key clinical takeaway

This trial adds mature randomized evidence supporting preoperative radiotherapy in selected high-risk gastric cancers. The improvements in DFS, OS, and locoregional control may influence perioperative treatment strategies, particularly in patients with bulky nodal or locally advanced disease.

RC48-C027: Disitamab vedotin-based combinations in HER2-expressing gastric cancer

→ LBA4026: Peng Z, Li C, Wang X, et al. Disitamab vedotin (DV) plus toripalimab (Tor) and chemotherapy (Chemo)/trastuzumab (Tra) for first-line (1L) HER2-expressing locally advanced or metastatic (la/m) gastric cancer (GC): Updated results from the RC48-C027 trial. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026

Updated results from RC48-C027 (NCT05980481) evaluated Disitamab vedotin plus Toripalimab with chemotherapy or trastuzumab in first-line HER2-expressing advanced gastric or gastroesophageal junction cancer. The study explored distinct strategies for HER2-high and HER2-intermediate/low disease. Earlier analyses reported ORRs of 82.4% for disitamab vedotin + toripalimab + trastuzumab in HER2-high disease and 72.0% for disitamab vedotin + toripalimab + CAPOX in HER2-intermediate/low disease. At the updated cutoff, investigators reported durable responses, clinically meaningful PFS improvement, and a favorable OS trend in both DTT and DTCr arms, with no new safety signals.

Key clinical takeaway

These data continue to support HER2-directed ADC strategies beyond conventional HER2-positive definitions. Although still phase II, the study may help expand biomarker-driven treatment approaches in gastric cancer, particularly for HER2-low and intermediate populations.

Esophageal squamous cell carcinoma 

SCIENCE: Neoadjuvant immunotherapy strategies in resectable ESCC

→ LBA4082: Leng X, Gong L, Lyu J, et al. Pathological complete response and ctDNA analyses in SCIENCE: Results from a randomized, phase III trial of neoadjuvant chemotherapy plus sintilimab and chemoradiotherapy plus sintilimab versus chemoradiotherapy in resectable locally advanced esophageal squamous cell carcinoma. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026

The SCIENCE trial (NCT05244798) compared neoadjuvant chemotherapy plus Sintilimab, neoadjuvant chemoradiotherapy plus sintilimab, and chemoradiotherapy alone in resectable locally advanced Esophageal squamous cell carcinoma. Among 307 evaluable patients, pathologic complete response (pCR) rates were 18.0%, 57.3%, and 49.0%, respectively. Compared with chemotherapy plus sintilimab, pCR was significantly higher with chemoradiotherapy plus sintilimab (OR 6.1; p<0.0001) and chemoradiotherapy alone (OR 4.4; p<0.0001). ctDNA analysis showed that preoperative positivity was higher after chemotherapy plus sintilimab (78.6%) compared with the other two arms (40.0% and 32.4%). Patients with ctDNA clearance had higher pCR rates (62.2% vs 9.1%).

Key clinical takeaway

The data suggest that chemoradiotherapy remains an important component of neoadjuvant treatment in ESCC, even in the immunotherapy era. The ctDNA findings are also notable and may inform future response-adaptive strategies.

This content has been developed independently by Touch Medical Media for touchONCOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (ChatGPT 5.5 [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.

Cite: Gastrointestinal oncology at ASCO 2026: Six key late-breakers. touchONCOLOGY. 17th June 2026.

Editor: Sophie Nickelson.