Dirk Arnold, MD, PhD is Director of the Asklepios Tumorzentrum Hamburg, a network cancer centre serving 7 community hospitals in Hamburg, and also Head of the department of Oncology, Haematology and Palliative Care at AK Altona, Hamburg

Yelena Y. Janjigian, MD, is chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center.

GI Cancer Experts on Notable Updates Shared During the 2025 ASCO Annual Meeting

We spoke with the following investigators in the field of gastrointestinal (GI) cancer to get their perspective on the most significant updates in the space shared during the 

Dirk Arnold, MD, PhD, the director of the Asklepios Tumorzentrum Hamburg and the head of the Department of Oncology, Hematology, and Palliative Care at AK Altona.

Kohei Shitara, MD, the director of the Department of Gastrointestinal Oncology at National Cancer Center Hospital East.

Yelena Y. Janjigian, MD, the chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center.

Ronan J. Kelly, MD, the chief of oncology, the W.W. Caruth, Jr. Chair in Immunology, and the founder and director of the Texas Cancer Interception Institute at Baylor Scott & White Health.

Vincent Picozzi, MD, a medical oncologist at Virginia Mason Franciscan Health.

During the meeting, there were several notable updates, including positive data with the addition of atezolizumab (Tecentriq) to chemotherapy as adjuvant treatment for patients with deficient mismatch repair colorectal cancer (CRC) in the phase 3 Alliance A021502; ATOMIC trial (NCT02912559), Arnold said. It was also impressive to see how the addition of targeted agents to chemotherapy improved outcomes for patients with CRC harboring 

Shitara and Janjigian both highlighted findings from the phase 3 MATTERHORN study (NCT04592913), which evaluated durvalumab (Imfinzi) plus FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) in patients with resectable gastric/gastroesophageal junction (GEJ) cancer. Findings from the study showed that patients who received the combination (n = 474) experienced a median event-free survival that was not reached (NR; 95% CI, 40.7-NR) vs 32.8 months (95% CI, 27.9-NR) among patients who received placebo plus FLOT (n = 474; HR, 0.71; 95% CI, 0.58-0.86; log-rank 

 < .001). These findings further cemented FLOT as the best systemic regimen for this patient population and it was encouraging to see investigators build on this efficacy with the addition of durvalumab, Janjigian said.

Data from the phase 3 DESTINY-Gastric04 trial (NCT04704934) firmly position fam-trastuzumab deruxtecan (T-DXd; Enhertu) as a standard-of-care option in the second line for patients with unresectable or metastatic HER2-positive gastric/GEJ adenocarcinoma. Findings from the study showed that patients who received T-DXd experienced a significant overall survival benefit compared with those treated with ramucirumab (Cyramza) plus paclitaxel (HR, 0.70; 95% CI, 0.55-0.90; 

During the meeting, there were several presentations that examined artificial intelligence–supported approaches, which was notable, Picozzi said. Pancreatic cancer research is also attracting a lot of attention from investigators across the world, he added.

Videos

Expert investigators in GI cancers share their perspectives on the most significant updates in the space shared during the 2025 ASCO Annual Meeting.

ARNOLD

"The OrigAMI-2 trial is now the proof of concept…trying to define a new standard of care."

Dirk Arnold, MD, PhD, a professor of oncology and gastrointestinal cancer expert at the University of Hamburg in Germany, discussed the rationale and potential clinical implications of the ongoing phase 3 OrigAMI-2 trial (NCT06662786), which is evaluating subcutaneous amivantamab-aamt (Rybrevant) vs intravenous (IV) cetuximab (Erbitux), both in combination with investigator’s choice of FOLFOX or FOLFIRI, as first-line treatment for patients with left-sided, 

 wild-type metastatic colorectal cancer (mCRC).

OrigAMI-2 is currently enrolling with a target accrual of over 1000 patients across more than 200 international sites. The trial is designed to assess progression-free survival (PFS) by blinded independent central review as the primary end point. Key secondary end points include overall survival, investigator-assessed PFS, objective response rate (ORR), duration of response, time to subsequent therapy, curative resection rate, and patient-reported outcomes. Patients are stratified by chemotherapy backbone, prior adjuvant therapy, and extent of disease.

Subcutaneous amivantamab, a bispecific EGFR/MET-targeted antibody co-formulated with recombinant human hyaluronidase PH20, is also being evaluated for its administration route, which may offer improved convenience and a more favorable safety profile compared with traditional IV therapies. In OrigAMI-2, subcutaneous amivantamab is dosed at 1600 mg weekly during the first cycle (2240 mg for patients ≥80 kg), followed by biweekly dosing. IV cetuximab is administered at 500 mg/m² biweekly or 400 mg/m² followed by 250 mg/m² weekly per investigator discretion.

According to Arnold, current standard of care for this patient population involves chemotherapy plus anti-EGFR therapy, typically cetuximab or panitumumab. However, resistance mutations frequently emerge early with selective EGFR blockade. Arnold noted that amivantamab’s mechanism of action may help delay the onset of acquired resistance, potentially improving response durability and long-term outcomes.

Arnold emphasized that OrigAMI-2 is one of the largest trials in mCRC to date and is designed to inform a potential shift in the frontline treatment paradigm. He also noted that the trial complements OrigAMI-3, a second-line study evaluating amivantamab in the same molecular subgroup. Collectively, these trials may define the future role of amivantamab across multiple lines of therapy in patients with 

Dirk Arnold, MD, PhD, on the investigation of amivantamab vs cetuximab, both in combination with chemotherapy, in RAS/BRAF wild-type mCRC.

Dr Arnold on the Evaluation of Chemo With Amivantamab or Cetuximab in RAS/BRAF Wild-Type mCRC

Dirk Arnold, MD, director, Department of Medical Oncology at Klinik für Tumorbiologie, Freiburg, Germany, discusses the phase IIIb CONSIGN study, which looked at treatment with regorafenib for previously treated patients with metastatic colorectal cancer (mCRC).

The CONSIGN trial reported on 2,872 patients from more than 180 institutions; it is a truly worldwide initiative, said Arnold. In this "real world" experience, the median treatment duration with regorafenib was 2.5 months. Patients received a median of 3 cycles of regorafenib (range, 1—33) at a median daily dose of 160mg (range, 74–166).

The trial was a follow-up to the phase III CORRECT trial, which demonstrated a median progression-free survival (PFS) of 2.0 months with regorafenib compared with 1.7 months with placebo (HR, 0.49; 95% CI, 0.42-0.58; 

 <.0001). Based on findings from this study, the FDA approved regorafenib in September 2012. 

The CONSIGN trial confirmed the results of the CORRECT trial, demonstrating a median PFS of 2.7 months (95% CI, 2.6-2.7). Adverse events were also similar between the two studies. Overall, 87% of patients required dose modifications, with 46% experiencing an adverse event that required a dose reduction.

View more from the 2015 European Cancer Congress

Dirk Arnold, MD, Director Department of Medical Oncology at Klinik fÃ¼r Tumorbiologie, Freiburg, Germany, Arnold Discusses the CONSIGN Study.


Dr. Dirk Arnold Discusses the CONSIGN Study

Dirk Arnold, MD, director of the Department of Medical Oncology at Klinik für Tumorbiologie, Freiburg, Germany, discusses the phase III Sirflox study, which looked at selective internal radiation therapy (SIRT) using Yttrium-90 (Y-90) resin microspheres for the treatment of metastatic colorectal cancer.

The trial included 530 randomized patients, half that received standard chemotherapy, which is FOLFOX6 with or without bevacizumab. The other half received Y-90 SIRT, which was given after the first or second administration of FOLFOX6 with or without bevacizumab. This treatment is for the palliative patient, said Arnold.

The results were surprising, said Arnold. There was no improvement in progression-free survival when all patients were taken into consideration. However, progression of the liver was significantly reduced with SIRT. This may be because many of the patients in the trial had disease in more than just the liver, which was not effected by the SIRT, said Arnold.

View more from the 2015 World GI Congress

 Dirk Arnold, MD, director of the Department of Medical Oncology at Klinik fÃ¼r Tumorbiologie, Freiburg, Germany, discusses the phase III Sirflox study, which looked at selective internal radiation therapy (SIRT) using Yttrium-90 (Y-90) resin microspheres for the treatment of metastatic colorectal cancer.

Dr. Dirk Arnold on Sirflox Study Results in Colorectal Cancer

Dirk Arnold, MD, director, Department of Medical Oncology, Tumour Biology Centre, Freiburg, Germany, discusses a phase III trial looking at options for maintenance therapy for metastatic colorectal cancer (mCRC). This study was presented at the ESMO 16th World Congress on Gastrointestinal Cancer.

There is currently some uncertainty as to how to use maintenance therapy after standard induction chemotherapy. Patients on this trial were randomized to continue to receive fluoropyrimidine and bevacizumab, bevcizumab alone, or to discontinue treatment.

When considering re-induction, Arnold says, bevacizumab alone as maintenance was not inferior to standard 5FU plus bevacizumab. Discontinuing treatment was inferior.

When considering time from randomization to first progression, the best option was 5FU plus bevacizumab, followed by bevacizumab alone. Discontinued treatment was the worst option, Arnold says.

Researchers concluded that maintenance therapy with any fluoropyrimidine and bevacizumab should be continued until first progression.

Dirk Arnold, MD, director, Department of Medical Oncology, Tumour Biology Centre, Freiburg, Germany, discusses a phase III trial looking at options for maintenance therapy for metastatic colorectal cancer (mCRC).

Dr. Arnold on a Phase III Trial Examining Options for Maintenance Therapy in mCRC

Dirk Arnold, MD, director of the University Cancer Center Hamburg at the University Medical Center Hamburg-Eppendorf, in Germany, discusses results of a phase III randomized trial that continued bevacizumab (Avastin) plus standard chemotherapy into the second-line for patients with metastatic colorectal cancer (mCRC).

The trial enrolled 820 patients with mCRC who had progressed after receiving bevacizumab plus an oxaliplatin- or irinotecan-based chemotherapy. For a second-line therapy, patients on the trial were randomized to continue bevacizumab in combination with the opposite chemotherapy or chemotherapy alone.

The trial found a median overall survival of 11.2 months for the combination arm compared to 9.8 months for those receiving chemotherapy alone (HR = 0.81). Additionally, Arnold notes the continuation of bevacizumab did not result in additional toxicity.

Dr. Dirk Arnold, from the University Cancer Center Hamburg, Germany, on Second-Line Bevacizumab Continuation Therapy for Metastatic Colorectal Cancer

Dirk Arnold, MD, PhD

Articles

GI Cancer Experts on Notable Updates Shared During the 2025 ASCO Annual Meeting

Dr Arnold on the Evaluation of Chemo With Amivantamab or Cetuximab in RAS/BRAF Wild-Type mCRC

Dr. Dirk Arnold Discusses the CONSIGN Study

Dr. Dirk Arnold on Sirflox Study Results in Colorectal Cancer

Dr. Arnold on a Phase III Trial Examining Options for Maintenance Therapy in mCRC

Dr. Arnold on Second-Line Avastin Continuation for mCRC