What are your top takeaways in GI Cancers from ASCO 2025?

1. MATTERHORN: it’s practice-changing and establishes durvalumab/FLOT as the new standard for perioperative therapy for gastric cancer
   
   
2. DESTINY-Gastric04: it confirms the superiority of 2L trastuzumab deruxtecan vs. ramucirumab/paclitaxel for HER2-positive gastric CA.
   
   
3. CHALLENGE study in colorectal CA: this is an incredibly difficult study to enroll in, and the results are, to me, more practice-changing than any novel therapy. It is virtually free – or costs no more than a gym membership – and has no toxicities!
   I’m surprised and disappointed it wasn’t part of the plenary session.
   
   
4. CT041-ST-01: this is the first study to show a benefit for a CAR T cell therapy in any solid tumor. While the results are modest and the study succeeded because 3L che...

1. ATOMIC - adding atezolizumab checkpoint inhibitor for 1 year to 6 months of adjuvant FOLFOX is the new standard of care for MSI-High stage III colon cancer.
   
   
2. MATTERHORN trial - adding durvalumab to perioperative FLOT in resectable gastric adenocarcinoma significantly improved event-free survival and is the new standard of care for early-stage gastric adenocarcinoma.
   
   
3. BREAKWATER - BRAF-mutated colorectal cancer carries a poor prognosis. Adding targeted therapy with encorafenib and cetuximab to chemotherapy in front-line setting significantly improved survival and is the new standard of care for advanced BRAF-mutated colorectal cancer.

1. The MATTERHORN study has redefined the perioperative treatment of resectable gastric cancer. It is now beautifully simple. Anywhere from the top of the esophagus to the bottom of the stomach, if a person has a resectable squamous cell carcinoma, then they should be treated c/ neoadjuvant chemoXRT (the CROSS regimen), followed by surgery, followed (as long as they do not have a complete pathologic response) by adjuvant IO. If, on the other hand, they have an adenocarcinoma, then they should be treated c/ periop D-FLOT as per the MATTERHORN trial. While this approach involves a slight amount of extrapolation (to adenocarcinomas of the esophagus), it seems the simplest and best way to incorporate all available data.
   
   
2. The ATOMIC trial demons...

As a gastrointestinal medical oncologist, it was very gratifying that 2 of the plenary session presentations provided the results from randomized gastrointestinal trials, including an NCI cooperative group study.

1. The first plenary presentation was a late-breaking abstract for a trial coordinated by the Alliance NCI cooperative group for patients with deficient DNA mismatch repair stage III colon cancer, randomizing patients to receive mFOLFOX with or without atezolizumab (ATOMIC trial). This study showed that the addition of atezolizumab to mFOLFOX improved 3-year DFS (86.4% versus 76.6%, HR, 0.50) and therefore the combination has become a new standard of care for this population of patients. The discussant for this abstract, Dr. Myriam Ch...

There are quite a few interesting/important GI studies reported at the ASCO Annual meeting, and here are several studies I personally felt may change my practice.

1. ATOMIC study: adding atezolizumab to adjuvant FOLFOX treatment showed clear disease-free survival for dMMR stage III colon cancer patients. Patients with resected dMMR 3 colon cancers were randomized to standard of care adjuvant mFOLFOX for 6 months versus the study arm with adjuvant mFOLFOX for 6 months with concurrent atezolizumab and additional 6 months of atezolizumab alone (for a total of 1 year of atezolizumab). Three-year disease-free survival for the study arm was 86.4% compared to the standard of care arm, 76.6% (HR 0.53, 95% CI 0.36-0.79, p=0.0007). The study arm had m...

1. ATOMIC trial – culmination of an outstanding national effort to investigate the use of an anti-PDL1 as ADJUVANT therapy combined with chemotherapy for MSI-High stage III colon cancer. The results show a major benefit for the addition of ICI therapy – i.e., 10% improvement in 3-yr DFS. Next study needs to be ICIs alone versus ICIs with chemotherapy.
   
   
2. CheckMate 8HW – long-term results of ipilimumab and nivolumab for MSI-High advanced CRC. Compared to chemo HR for PFS was a shocking 0.21. Who has ever seen an HR like this?? Also, even if one started with chemo and crossed over to ICIs, there was still a lesser benefit. So, order of treatment does matter, and combined anti-PD(L)-1 plus anti-CTLA4 should be the preferred first-line therapy for s...

1. CheckMate 8HW

Building on what we already know, the expanded analyses of NIVO + IPI vs NIVO (all lines) and longer follow-up results for NIVO + IPI vs chemo were presented.

Not surprisingly, and what has already been reported, 1L NIVO + IPI continued to show PFS benefit vs chemo.

Across all lines, NIVO + IPI demonstrated superior PFS vs NIVO with HR 0.62 (0.48-0.81); P = 0.0003. PFS2 favored NIVO + IPI vs NIVO across all lines of therapy with HR 0.57 (0.42–0.78).

Very importantly, in all treated patients, grade 3/4 treatment-related adverse events occurred in 78 (22%) and 50 (14%) pts in the NIVO + IPI and NIVO arms, respectively.

These data continue to reinforce immunotherapy as the frontline standard of care over chemotherapy for this pa...

1. CASSANDRA - A phase II study of neoadjuvant PAXG (Abraxane, cisplatin, capecitabine, gemcitabine) superior to FOLFIRINOX for borderline or resectable pancreatic ductal adenocarcinoma in terms of Ca 19-9 response, stage, N0 resection, and disease control. (Reni et al, non-colorectal oral abstracts) I am discussing this regimen with my patients now, and we eagerly await the final survival results at future meetings.
   
   
2. Sinicrope et al. and the ATOMIC study sets a new standard of care for stage III dMMR/MSI-high colon cancer with adjuvant atezolizumab/FOLFOX – the future questions are if the chemo is really needed, or could immunotherapy be enough?
   
   
3. One that may have been overlooked is the POLCAGB trial – a randomized phase 3 study where neoadjuv...

1. BREAKWATER survival data
   
   
2. Exercise in colon cancer
   
   
3. ATOMIC in colon cancer

1. The phase III MATTERHORN study evaluated durvalumab (Imfinzi) combined with perioperative FLOT chemo in operable gastric and GEJ cancers. It showed a significant boost in 2-year overall survival from ~70% to ~76% in the Imfinzi arm without added toxicity. This supports the adoption of FLOT + durvalumab as standard of care now and perhaps will encourage integrating immunotherapy with other earlier regimens as well, not just in metastatic disease.
   
   
2. The ATOMIC trial was a phase III randomized trial (Alliance A021502, NCT02912559) comparing standard mFOLFOX6 chemotherapy alone versus mFOLFOX6 plus atezolizumab, followed by one year of atezolizumab monotherapy, in resected stage III colon cancer with deficient mismatch repair (dMMR/MSI-high). 71...

1. ATOMIC

This was a phase III study that examined patients who were MMR-deficient (MSI-High) with stage III colon adenocarcinoma who underwent resection, and were randomized to receive either FOLFOX for 6 months vs FOLFOX for 6 months + Atezolizumab for 1 year. Slightly over half of the patients had ‘high risk’ (T4 and/or N2) disease. There was a significant improvement in 3-year disease-free survival (DFS) with the addition of atezolizumab from 76.6% (FOLFOX) to 86.4% (FOLFOX + atezolizumab), HR 0.50 (95%CI 0.34-0.72), p<0.0001. OS data is not yet mature, and may possibly be impacted by subsequent receipt of immunotherapy for patients in the FOLFOX alone arm. The combination was generally well tolerated. For MSI-H stage III colon cancer pa...

1. I believe ATOMIC does establish a new standard of care for adjuvant atezolizumab in mismatch repair-deficient stage III colon cancer, but outstanding questions remain: a) does the chemotherapy backbone have to be 6 months of FOLFOX even for T3N1 tumors? b) Would other immunotherapy (specifically PD-L1 inhibitors) work in the same setting? c) Would neoadjuvant immunotherapy a la NICHE-2 confer the same longitudinal benefit beyond upfront pathologic response?
   
   
2. CHALLENGE is a triumph for structured exercise as its own non-pharmacological adjuvant therapy for stage III colon cancer as it adds a 5-year disease-free survival benefit of ~6% beyond health education alone; this should both empower patients that they have agency over their post-di...

1. The CHALLENGE trial: In this phase 3 randomized trial, patients with resected CRC who had completed adjuvant chemotherapy were assigned to either a 3-year structured exercise program (exercise group) or to receive health-education materials alone (health-education group). Patients were selected to be sedentary at baseline. The goal was to get them to at least +10MET-hours/week=150 min/week of brisk walking (brisk means about 3.5 MPH on a treadmill).
The primary endpoint was DFS. At a median follow-up of 7.9 years, DFS was significantly longer in the exercise group. The 5-year DFS rate was 80.3% in the exercise group versus 73.9% in the health-education group (HR 0.72; P=0.02). Similarly, OS also favored the exercise group: an 8-year OS o...

1. MATTERHORN: This trial evaluated perioperative FLOT chemotherapy versus FLOT combined with durvalumab in patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. Notably, 90% of patients had PD-L1 expression and only 5% were MSI-H, reflecting a typical biomarker distribution. The pCR rate was 19% with durvalumab vs 7% with FLOT alone. Adding durvalumab led to a meaningful improvement in 24-month event-free survival (from 59% to 67%) and overall survival (from 70% to 76%). These results suggest that D-FLOT is likely to become the new standard of care for resectable gastric cancer and potentially for esophageal adenocarcinoma and GEJ tumors as well.
   
   
2. ATOMIC: This trial evaluated adjuvant therapy in stage III dMMR co...

MATTERHORN

Summary: Adding durvalumab to FLOT perioperatively improved 2-year event-free survival (67.4% vs. 58.5%; HR 0.71) in resectable gastric or GE junction adenocarcinoma, with a numerical OS improvement.

Comments:

• These findings specifically apply to adenocarcinoma; squamous cell carcinoma of the esophagus remains managed with definitive chemoradiotherapy.
• The optimal timing of immunotherapy-neoadjuvant vs. adjuvant remains uncertain. Notably, adjuvant nivolumab has shown PFS benefit in the setting of neoadjuvant chemoradiotherapy, followed by surgery in EC/GEJC (CheckMate 577), raising questions about combining or sequencing these strategies.
• Preservation of organ function and quality of life is critical, especially in the context of...