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

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

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.

Vincent Picozzi, MD, discusses the addition of TFields to gemcitabine and nab-paclitaxel in locally advanced pancreatic ductal adenocarcinoma

Dr Picozzi on the Addition of TTFields to Gemcitabine and Nab-Paclitaxel in Locally Advanced PDAC

"The use of TTFields did produce a statistically significant improvement in overall survival over [chemotherapy alone]. This is important in that this is first positive trial ever in this stage of pancreatic cancer, and it also provides a foundation for additional therapy endeavors that leverage the use of TTFields."

Vincent Picozzi, MD, a medical oncologist at Virginia Mason Medical Center, discussed the clinical relevance of data from the phase 3 PANOVA-3 trial (NCT03377491) evaluating the addition of tumor-treating fields (TTFields) to gemcitabine and nab-paclitaxel (Abraxane) in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC).

Results from PANOVA-3 presented at the 2025 ASCO Annual Meeting demonstrated that the TTFields regimen generated a statistically significant overall survival (OS) benefit over chemotherapy alone (HR, 0.82; 95% CI, 0.68-0.99; 

 = .039). Specifically, TTFields plus chemotherapy produced a median OS of 16.2 months (95% CI, 15.0-18.0) compared with 14.2 months (95% CI, 12.8-15.4) for chemotherapy alone. The 1-year OS rates were 68.1% (95% CI, 62.0%-73.5%) and 60.2% (95% CI, 54.2%-65.7%), respectively (

This study represents the first positive phase 3 trial in the locally advanced PDAC patient population, Picozzi noted. He said that these data provide a foundation for further exploration of TTFields in PDAC and may inform future strategies incorporating the device into standard treatment paradigms.

PANOVA-3 enrolled patients with unresectable, locally advanced PDAC who had not received prior systemic therapy and were ineligible for immediate surgical resection or radiation. Participants were randomly assigned to receive either standard-of-care chemotherapy with gemcitabine and nab-paclitaxel alone or in combination with TTFields, which delivers low-intensity, alternating electric fields via a wearable device that disrupts mitotic activity in tumor cells.

In addition to OS outcomes, quality-of-life (QOL) metrics favored the TTFields arm. Improvements were observed in global health status and patient-reported pain measures, as well as prolonged time to deterioration in pain. Picozzi emphasized that in pancreatic cancer, where treatment options are limited and the symptom burden is high, QOL outcomes are particularly important and may be as clinically meaningful as traditional survival end points.

Vincent Picozzi, MD, discusses the addition of TFields to gemcitabine and nab-paclitaxel in locally advanced pancreatic ductal adenocarcinoma.

Vincent J. Picozzi Jr, MD, director, Pancreas Center of Excellence, physician, Division of Hematology-Oncology, Virginia Mason Medical Center, discusses the prognostic value of pathologic response to neoadjuvant chemotherapy in patients with resected pancreatic cancer.

The goal of treatment in localized pancreatic cancer is cure, says Picozzi. As such, implementing chemotherapy and chemoradiation in conjunction with surgery is necessary to maximize the chance of cure for patients.

However, the use of chemotherapy and chemoradiation in the neoadjuvant setting can make it difficult to determine optimal adjuvant therapy, explains Picozzi.

At the 2020 Gastrointestinal Cancers Symposium, a poster was presented on the impact of neoadjuvant chemotherapy on treatment outcomes in patients with resected pancreatic cancer.

A univariate analysis of 134 eligible patients confirmed that many variables, including pathologic response to neoadjuvant chemotherapy, have prognostic significance for overall survival. However, a multivariate analysis revealed that other factors such as tumor size, nodal involvement >20%, and tumor differentiation were independent variables that did not have prognostic value.

As such, building upon these data may shed light on how to optimize clinical decisions regarding adjuvant therapy for patients with pancreatic cancer, concludes Picozzi.

Vincent J. Picozzi Jr, MD, discusses the prognostic value of pathologic response to neoadjuvant chemotherapy in patients with resected pancreatic cancer. 


Dr. Picozzi on Prognostic Value of Pathologic Response to Chemo in Pancreatic Cancer

Vincent J. Picozzi, MD, director, Pancreatic Center of Excellence, Virginia Mason Medical Center, discusses the use of SM-88 in pancreatic cancer.

SM-88 is an oral therapy, and unlike traditional therapies in pancreatic, it is not a chemotherapy. The novel anticancer regimen is comprised of a tyrosine derivative (D,L-alpha-metyrosine), an mTOR inhibitor (sirolimus), a CYP3a4 inducer (phenytoin), and an oxidative stress catalyst (methoxsalen). The agent has shown promising activity with little toxicity for patients with metastatic pancreatic cancer who have progressed on at least 1 prior line of therapy. Due to the agent’s tolerability, elderly and frail patients are also able to receive the treatment. Physicians and patients alike are eagerly awaiting more data to further prove the agent’s efficacy, says Picozzi.

A physicist came up with the construction of SM-88, adds Picozzi. The agent uses a derivative of an immunoacid tyrosine as a “poisonous pill” to cancer cells. By redirecting the mTOR inhibitor, CYP3a4 inducer, and oxidative stress catalyst, the agent is able to enhance the effect of the altered tyrosine, explains Picozzi.

Vincent J. Picozzi, MD

Articles

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

Dr Picozzi on the Addition of TTFields to Gemcitabine and Nab-Paclitaxel in Locally Advanced PDAC

Dr. Picozzi on Prognostic Value of Pathologic Response to Chemo in Pancreatic Cancer

Dr. Picozzi on the Use of SM-88 in Pancreatic Cancer