OncologyTube: [00:00:00] Okay, we’re here at ASCO GI 2024 and we have Dr. Ethan Ludmir, medical doctor and the assistant professor, Department of Gastrointestinal Radiation Oncology, Division of Radiation Oncology, the University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Ludmir, thank you for joining us
Ethan Ludmir, MD: today.
Thank you for having me.
OncologyTube: Today we’ll be discussing addition of metastasis directed therapy to standard of care systematic therapy of oligometastatic pancreatic ductal adenocarcinoma. Results of a multicenter randomized phase 2 trial, which is being featured here at ASCO GI 2024. So, Dr. Ledmeyer, can you provide an overview of the EXTEND
Ethan Ludmir, MD: trial?
Of course, thank you so much for having me, Alan. The EXTEND trial was a multi center trial assessing the role of local therapy, things like [00:01:00] radiation therapy, for patients who have what we call oligometastatic disease, which is to say they have disease that has spread from beyond where that primary tumor started, but the number of sites of disease that are metastases are few.
In our trial, we define that as having five or fewer spot sites of metastatic disease outside of the primary tumor. So for patients on our trial, they were randomized to either standard of care systemic therapy, which can include things like chemotherapy, immunotherapy, or the like, or local therapy, metastasis directed therapy, things like radiation, to all of those spots, and then they’d move on to systemic therapy.
And the question was whether or not by adding that local therapy, by adding metastasis directed therapy, do we improve patients progression free survival. This trial was a basket design, meaning we ran this trial for many different folks. There’s a cohort for patients with breast cancer, a cohort for patients with prostate cancer, and here today at ASCO GI, we present the results of patients with pancreas cancer.[00:02:00]
OncologyTube: Alright, so what were the key findings from the EXTEND trial regarding the use of metastasis directed therapy in combination with systematic therapy for patients with oligo metastatic pancreatic ductal adenocarcinoma, otherwise known as PDAC, particularly in terms of progression free
Ethan Ludmir, MD: survival? Thank you for the question.
So the primary end point of the trial was progression free survival. We found that by adding metastasis directed therapy, that we markedly improved progression free survival for patients, from a median progression free survival time of 2. 5 months for patients on the control arm getting systemic therapy alone, to 10.
3 months for patients getting the metastasis directed local therapy with systemic therapy.
OncologyTube: Can you elaborate on the safety profile of comprehensive metastasis directed therapy in the trial? Were there any significant adverse events associated with MDT? And how did they compare to the control group [00:03:00] receiving systematic therapy alone?
Ethan Ludmir, MD: Terrific question. The safety profile of adding metastasis directed therapy was exceedingly positive. One grade two toxicity was observed related to MDT in the experimental arm, and that was a patient who developed radiation esophagitis after getting radiation from mediastinal lymph nodes as a site of metastatic disease.
This resolved with supportive measures, but otherwise no grade two or higher adverse events potentially related to MDT were observed in the trial, which reflects a favorable safety profile, particularly given the strong efficacy signal.
OncologyTube: Alright, so the study mentions increased systematic immune responses in the MDT arm.
Could you discuss the potential implications of these immune responses and how they might influence treatment landscape for PDAC?
Ethan Ludmir, MD: Terrific question. So translational endpoints that we looked at in this trial use peripheral blood from patients to examine whether or not, by [00:04:00] adding this local therapy, by adding radiation, we saw changes in the systemic immune profile, and the answer is we did.
When adding radiation, we saw a marked increase in highly active CD8 positive T cells, as well as increased cytokines like IL 15, and an expansion of what we call T cell receptor clonal repertoire. This reflects, potentially, that by adding radiation, you’re activating the systemic immune profile to potentially target cancer neoantigens out there in micrometastatic disease.
So it’s possible that by doing radiation, you’re actually conferring not only local control for the tumors that you irradiate, but potentially priming the pump for the immune system to be able to identify and surveil and prevent further growth of micrometastatic disease outside of the areas that receive radiation.
Okay,
OncologyTube: this has been an interview with Dr. Ethan Ludmir, a medical doctor and the assistant professor, Department of Gastrointestinal Radiation Oncology, Division of [00:05:00] Radiation Oncology, the University of Texas M. D. Anderson in Houston. Dr. Ludmyer, thank you so much for chatting with us today. Thank you so much for having me.
Ethan Ludmir, MD: pleasure.