Guiding Treatment Selection and Response Assessment in Metastatic Pancreatic Cancer
Daniel King, MD, PhD, Northwell Health, New Hyde Park, New York, discusses the evaluation of a patient with suspected metastatic pancreatic cancer seeking a second opinion to illustrate how molecular profiling can inform treatment selection and clinical trial eligibility.
He reviews the importance of obtaining existing molecular testing results, identifying actionable mutations, and considering clinical trials without unnecessarily delaying treatment. He also discusses serial imaging as the standard for assessing treatment response and the complementary roles of CA 19-9 and circulating tumor DNA in interpreting equivocal imaging findings.
Transcript:
Hello, my name is Dan King. I’m a medical oncologist and researcher at Northwell Health in New York. Today, I’d like to present a case about the use of molecular profiling and circulating tumor DNA for patients with metastatic pancreatic cancer.
Today’s case vignette is about our patient, Mr. Jackson. He’s a 65-year-old man with a past medical history of hypertension who presented for medical oncology consultation as a second opinion after recently being diagnosed with metastatic adenocarcinoma.
He initially sought attention for a persistent nonproductive cough that had been present for many weeks. He otherwise reported a decline in energy over the last 2 to 3 months, some mild unintentional weight loss, and reduced appetite, but he denied hemoptysis, fevers, or significant abdominal pain. He remained independent in his activities of daily living.
The initial imaging, which was performed at an outside health system, demonstrated widespread bilateral pulmonary metastatic lesions as well as a mass in the tail of the pancreas, which was concerning for a pancreatic primary with metastatic disease. He subsequently underwent an interventional radiology-guided biopsy of a lung lesion, and the pathology showed adenocarcinoma with an IHC profile of CK7 positivity, which was interpreted as being most consistent with an upper GI or hepatobiliary primary. In the context of the pancreatic tail mass seen on imaging, the working diagnosis was metastatic adenocarcinoma, likely pancreatic in origin.
He presented to our office, accompanied by his spouse, for a second opinion regarding diagnosis, prognosis, and treatment options. He mentioned that he’s particularly interested in targeted therapy and whether he might be a candidate for the recently approved daraxonrasib medication. He asked about the role of genomic profiling to identify actionable mutations.
He was eager to understand whether additional molecular testing, pathology review, or repeat biopsy would help guide treatment selection. He wanted to know how we would measure the disease in terms of repeat imaging and blood tests to know if the treatment was working.
With that case vignette, I have a quiz questions that I’d like to review that I think help highlight some of the important questions surrounding the proper management of this case.
The question is: What is the most appropriate next step regarding molecular profiling and treatment selection?
Recall, this is the patient who came to us for a second opinion. We believe molecular profiling was already done at the outside institution. The possible answers are:
A. Obtain molecular testing results from the outside medical system and then start him on daraxonrasib only if he has a KRAS mutation.
B. Given that the FDA label for daraxonrasib is not biomarker-selected, molecular profiling is not necessary, and he can start daraxonrasib now.
C. Obtain molecular testing results from the outside medical system and then offer to help the patient find a clinical trial based on any mutations found.
D. Reorder molecular profiling now and wait for the results to come back before providing a recommendation for therapy.
Having heard those candidate answers, I’d like to go through each one and give you my take as to whether I think that’s the right answer.
Answer A was about obtaining molecular test results from the outside system and starting him on daraxonrasib only if he has a KRAS mutation. In that case, I don’t think that’s the best answer because daraxonrasib is now FDA-approved regardless of mutation. Meanwhile, he is eligible for first-line therapy. He’s a robust, fit guy and would not be on-label treatment for daraxonrasib.
Answer B is about the FDA label for daraxonrasib not being biomarker-selected. Biomarker testing is not needed, and you can start daraxonrasib now. That also, I think, is not the best answer, again, because he’s eligible for first-line therapy.
Answer C is to obtain molecular testing results from the outside system and then offer the patient a trial. I like that answer because it’s best to know, first of all, what type of mutation he has. He may have a mutation that, for example, could be an eligibility criterion for a clinical trial in the first-line setting.
For example, the RASolute 303 study, which is underway right now, is a first-line phase 3 trial, a three-arm trial in which patients are randomized to chemotherapy, chemotherapy with a RAS inhibitor, or a RAS inhibitor alone. Secondly, there are at least two first-line phase 3 clinical trials looking at G12D inhibitors. If this patient were to have a G12D mutation, he could potentially be a candidate for that trial and get on that trial.
Then answer D is to reorder molecular profiling now and wait for the results to come back before providing a recommendation for therapy. I don’t think that’s the best answer either. The reason is that, first of all, if you reorder molecular profiling for a patient who already had molecular profiling done, we have to justify to insurance why we’re doing a second test, which may lead to out-of-pocket costs.
I also don’t think it’s right necessarily to wait for the results to come back from molecular profiling. That really should only be considered if you expect the results to come back very soon, because it would be detrimental to wait too long for the results instead of getting the patient on therapy.
Those are my answers, that was my vignette. I appreciate your listening today. Thank you.
