When Science is Making a Breakthrough, How Can Patients Act Upon It?
An Ask the Expert conversation with Dr. Noelle LoConte, in partnership with the Pancreatic Cancer Action Network (PanCAN)
"For a patient with resected pancreatic ductal adenocarcinoma and an R1 margin, would you recommend banking the tumor tissue and performing comprehensive genomic profiling now, so that if new KRAS-targeted adjuvant trials open in the next year or two, the patient could potentially be eligible without repeating testing?"
This question set the tone for Dr. Noelle LoConte, GI Oncologist with the Department of Medicine, University of Wisconsin–Madison. In July 2026 she joined Smart Patients for an Ask the Expert (ATE) on KRAS and pancreatic cancer. This ATE session was a follow-up to the Pancreatic Cancer Action Network's recent webinar on the same topic. The question was about timing – whether there's something that can be done now to position yourself for a trial that doesn't yet exist. Dr. LoConte confirmed that "doing profiling now makes a lot of sense, given that the R1 margin does predict for a high likelihood of recurrence." She added that once a patient is more than 12 weeks past surgery, treatment is no longer technically "adjuvant." It's first-line therapy for recurrence, so getting the profiling started early means the result is ready by the time it's needed, not later on.
Because the science behind pancreatic cancer treatment is advancing, patients are planning several moves ahead to anticipate testing turnaround times, trial openings, and insurance shifts. Almost everything discussed in this ATE – from biomarker basics to a promising new drug – was characterized by the gap between what's practical right now and what might become possible soon.
What is KRAS?
Dr. LoConte opened with an introductory explanation that KRAS is a gene altered in the large majority of pancreatic ductal adenocarcinomas (PDAC). The mutation lives in the tumor itself, not in a patient's inherited DNA. As she noted, this means "there is no risk in passing this along to your children/progeny."
The most common alteration in PDAC is KRAS G12D, detected through next-generation sequencing (NGS) of the tumor, or sometimes by circulating tumor DNA.
Mutated KRAS was long considered "undruggable," but a recent scientific breakthrough is changing that. Dr. LoConte described daraxonrasib, an oral pan-RAS inhibitor now available through an Expanded Access Program ahead of FDA approval. "Daraxonrasib doubled the survival against chemo," she said. "It did not seem to matter which KRAS mutation the tumor had; response was seen in all." The RASolute-302 trial, presented at the 2026 ASCO Annual Meeting, was a randomized, controlled Phase 3 study comparing daraxonrasib with standard second-line chemotherapy in metastatic PDAC. (Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer | New England Journal of Medicine) On August 26, 2026, the FDA approved RASONQUE™ (daraxonrasib). Median overall survival was 13.2 months with daraxonrasib versus 6.7 months with chemotherapy. (Note: Half the people lived longer than that. In a study, each median is the number that half the participants fall short of and half exceed.)
Dr. LoConte cautioned, "[Daxaronasib] is not a cure. Patients eventually would have progression." Then she flagged that it's only been studied specifically in second-line, stage IV disease. Other settings, such as before surgery or first-line, are still in trials. This kind of detailed response helps patients understand what’s realistic considering their own circumstances.
When to Stop Waiting and Start Treatment
“How should patients time their testing before a second opinion? Does it take long to get results and if so, can a patient start treatment while waiting?”
The issue of "When do I need to know, and what do I do while I'm waiting to find out?" arose again with regard to tissue-banking.
Patients continue to look for guidance in the shifting treatment landscape to manage their care strategically as findings evolve about treating the KRAS mutation. Biomarker testing "does take a long time — 4 to 6 weeks for tissue-based platforms, about 2 weeks for peripheral blood-based ones,” said Dr. LoConte, “so yes, you often do want to start treatment before the results come back." Testing done at a first center usually transfers to further opinions without being repeated, since it's typically run by one of a handful of national labs. Also, repeat testing isn't always covered by insurance.
Turning Science Into Next Steps
Over the three days of conversation, in addition to discussing timing and access to new treatment, Dr. LoConte answered questions about daraxonrasib's side effects (mucositis, nausea, rash, diarrhea) and how new information on KRAS interacts with other cancers. Smart Patients members left with a broader understanding of the new science and with resources to figure out next steps:
Talk Test Take Control - Pancreatic Cancer Action Network or Biomarker and Tumor Marker Tests | American Cancer Society. These resources lay out when to test, how long results take, when it makes sense to start treatment before they're back, and how tissue banking works for patients considering a future trial.
Expanded Access Program. This explains what these programs are, who qualifies, and how a patient can raise this option with their oncologist. As Dr. LoConte noted, this process must be initiated by the treating doctor.
For participating patients, the immediate takeaways are concrete: If you have PDAC and haven't had broad NGS testing, it's worth having that conversation with your care team now regardless of where you are in treatment. If you're facing surgery, a second opinion, or a period of watchful waiting, it's good to ask specifically about the timing of testing, not just testing itself. For anyone weighing next steps, it's worth asking, "Is there a trial I can consider?"
This conversation both deepened the understanding of a mutation and provided guidance on navigating the sequence of decisions around it. Dr. LoConte saw how patients interact with science: as science moves, patients reflect findings against their own biology and current context to calibrate their hope in that science for their own future.
Thank you to PanCAN for helping to arrange this Ask the Expert Session and to Dr. LoConte for sharing her time and expertise with the Smart Patients community. Additionally, patients and caregivers can contact PanCAN Patient and Caregiver Services for additional information.