Pancreatic Cancer Research Highlights from ASCO GI 2025

IBBL; Flickr

The 2025 ASCO Gastrointestinal Cancer Symposium featured the breadth of GI cancers and as always, pancreatic cancer was well represented.  

Held in San Francisco from January 23rd to the 25th, the conference brought together some of the world’s leading GI oncology clinicians, physician-scientists, researchers, pharmaceutical leaders, and patient advocates to learn about the latest investigations and potential advances in patient care. As always, Let’s Win brings you some of the highlights of this year’s symposium; we will cover some in more depth during the year. Be assured that although more work needs to be done, progress in pancreatic cancer treatment is indeed being made.

Pan-RAS Inhibitor Shows Promise

Unlike RAS inhibitors that only target specific RAS mutations like KRAS G12C, pan-RAS inhibitors can block a wider range of RAS mutations, potentially improving treatment for more patients. An investigational pan-RAS inhibitor dubbed daraxonrasib (RMC-6236) shows early activity and has a manageable safety profile in patients with previously treated RAS-mutant pancreatic cancer. In this phase I study, 127 participants received RMC-6236 at doses ranging from 160 mg once daily to 300 mg once daily. The researchers saw early and deep decreases in RAS mutant circulating tumor DNA. Median progression-free survival for patients being treated in the second line was 8.5 months, and the median overall survival was 14.5 months. The researchers noted RASolute 302, a randomized phase III trial evaluating RMC-6236 as a second-line treatment versus chemotherapy in patients with metastatic pancreas cancer is ongoing.

Baseline Geriatric -and Quality of Life Factors Linked to Chemotherapy Survival

The GIANT study was the first elderly-specific clinical trial to evaluate chemotherapy in vulnerable adults with metastatic pancreatic cancer. Data from an oral presentation was based on results from the phase II ECOG-ACRIN EA2186 trial, which revealed a correlation between geriatric assessment/quality of life and overall survival related to several significant factors. These factors include activities of daily living, nutrition, and depression, among other quality-of-life measures. White blood cell counts, depression, and BMI significantly correlated with grade 3 toxicity incidence in a multivariate analysis. Results demonstrated no significant difference in median overall survival between the treatment arms, with overall survival of 4.7 months in the gemcitabine/nab-paclitaxel cohort and 4.4 months in the fluoropyrimidine-based cohort. The median progression-free survival was 3.0 months versus 2.4 months, respectively. However, among patients who received at least four weeks of therapy, median overall survival improved to 8.0 months. The study suggests that outcomes can be enhanced in this population by addressing baseline vulnerabilities, as well as improving quality of life and tailoring supportive care.

ctDNA Analysis and Treatment Monitoring in Advanced Disease

Circulating tumor DNA (ctDNA) analysis could potentially offer a quick and reliable method for monitoring treatment response in patients with advanced disease. A study, dubbed ARTEMIS-PC, evaluated a personalized, tumor-informed microscopic residual disease (MRD) assay, which tests for specific, tumor-derived genetic alterations, for the monitoring of responses to systemic therapy in patients with advanced pancreatic cancer.

The study enrolled 99 patients (median age 70) with previously untreated, unresectable stage III or IV pancreatic cancer. Personalized panels were created for 92 patients. The majority of participants (86 percent) received treatment with gemcitabine/nab-paclitaxel. At enrollment, 88 percent of patients were MRD-positive, and during follow-up, 40.7 percent achieved ctDNA clearance or conversion to MRD-negative status. This so-called clearance was associated with a higher objective response rate (61.5 percent vs 17.6 percent) and disease control rate (100 percent vs 64.7 percent.) They also had significantly longer progression-free survival (9.0 vs 3.5 months) when compared with patients without ctDNA clearance. The researchers say they are planning more studies with larger cohorts.

Patient Regret after Surgery Shows Need to Discuss Quality-of-Life Issues

Some patients with localized pancreas cancer who chose to undergo surgery say they have some regrets about their decision. Most of those regrets are related to quality-of-life issues. Study results show that 19 of 45, or 42.2 percent, of patients who underwent surgery, which remains the only potential cure for the disease, expressed this regret. Those who had complications at 30 days after the procedure were more likely to express regret, with 42.1 percent of these patients reporting regret, compared with those who experienced issues 90 days postoperatively, of whom just 15.4 percent reported regret. Both groups had similar baseline characteristics and recurrence rates at the time the survey was completed.

According to the authors, the regret could maybe be linked to preoperative counseling that did not emphasize the potential quality-of-life effects of surgery, or how long those effects could last. Study results also indicated that those expressing regrets had poorer physical function, with a mean score of 79.30 compared with 92.31 for those without regrets. The effect the surgery had on the patient’s social activities was also a factor, with those who had a mean score of 67.54 expressing regret versus those with a mean score of 84.67.

Impact of Real-World Dose Reductions of NALIRIFOX

Reduced doses of liposomal irinotecan (Onivyde) and oxaliplatin did not cause worse overall survival (OS) outcomes in patients with metastatic pancreatic cancer who were pretreated with liposomal irinotecan, oxaliplatin, 5-fluorouracil (5-FU), and leucovorin (NALIRIFOX). These results are from a post-hoc analysis of the phase III NAPOLI 3 trial presented at the symposium.

The analysis found that among patients in the NALIRIFOX arm who were part of the safety population, those who required dose reductions of liposomal irinotecan achieved a median OS of 12.6 months compared with 9.4 months in patients without a dose reduction of the agent. Similarly, dose reductions of oxaliplatin were associated with a median OS of 13.5 months compared with 7.7 months in patients who did not receive a dose reduction of oxaliplatin. Similar OS results were seen when looking at subgroups of patients treated in North America and the rest of the world. According to the authors, similar overall survival results were found among subgroups of patients treated in North America and worldwide.

Precision Promise Shows Strength of Bayesian Design

Precision Promise is a multicenter, phase II/III, innovative Bayesian adaptive platform trial sponsored by the Pancreatic Cancer Action Network (PanCAN). The trial tests multiple experimental arms efficiently and rapidly against common controls. Data shared at ASCO GI showed the results of pamrevlumab plus nab-paclitaxel/gemcitabine. The addition of pamrevlumab, which is an investigational antibody treatment, to chemotherapy did not show a benefit for patients with metastatic pancreatic cancer in Precision Promise. It also did not show benefit in another trial called LAPIS, designed for those with locally advanced disease. In Precision Promise, pamrevlumab plus nab-paclitaxel/gemcitabine was tested as first-line (Line 1) and second-line (Line 2) therapy for metastatic disease versus  nab-paclitaxel/gemcitabine.