Researchers from The College of Texas MD Anderson Most cancers Heart demonstrated that including metastasis-directed radiation remedy to standard-of-care chemotherapy improved progression-free survival (PFS) in sufferers with oligometastatic pancreatic most cancers. Findings from the multicenter EXTEND trial, revealed right this moment in the Journal of Scientific Oncology, had been first offered on the 2024 American Society of Scientific Oncology (ASCO) Gastrointestinal Cancers Symposium.
At a median follow-up of 17.3 months, PFS was 10.3 months in sufferers who acquired metastasis-directed remedy (MDT) plus chemotherapy in comparison with solely 2.5 months in those that acquired commonplace chemotherapy remedy. Moreover, elevated immune responses from MDT had been related to longer survival instances.
Sufferers with metastatic pancreatic most cancers have restricted remedy choices and poor outcomes. We’re excited to see that the addition of focused radiation remedy quadrupled the typical progression-free survival time, suggesting this strategy probably represents a paradigm shift in treating metastatic pancreatic most cancers.”
Ethan Ludmir, M.D., first writer assistant professor of Gastrointestinal Radiation Oncology
Metastatic pancreatic most cancers spreads quickly to important organs, posing important challenges for illness administration. Analysis typically happens at a sophisticated stage, decreasing remedy efficacy and reducing survival charges. The illness’s complexity and resistance to many therapies additionally contributes to its poor prognosis. Chemotherapy, the principle remedy possibility, usually gives a seven-month common survival time earlier than illness development.
MDT targets metastases with high-dose ablative radiation remedy, aiming to remove all most cancers cells in any respect websites recognized on a scan. This strategy is primarily being evaluated for sufferers with oligometastatic illness for whom imaging reveals 5 or fewer metastases. Oligometastatic illness is commonly described as an intermediate stage of most cancers, between a localized tumor and widespread most cancers.
MDT has emerged as a significant space of analysis after a profitable preliminary research at MD Anderson in 2016 demonstrated its effectiveness for sufferers with lung most cancers. It has since been proven to be efficient in a number of most cancers varieties, together with prostate and kidney most cancers.
EXTEND is a Section II randomized basket trial for a number of stable tumors, testing whether or not MDT plus chemotherapy improves PFS in contrast with chemotherapy alone for sufferers with oligometastatic most cancers. It’s the first randomized trial to particularly consider MDT for sufferers with oligometastatic pancreatic most cancers. Between 2019 and 2023, 40 sufferers with 5 or fewer metastatic websites had been evaluated within the pancreatic most cancers basket of the EXTEND trial.
The median time to new lesion recurrence was 14 months within the MDT arm versus 5 months within the management arm. The 12-month freedom from new lesion recurrence charge was 54% within the MDT arm and 38% within the management arm. Crossover from the management arm to MDT was allowed. MDT, which primarily consisted of high-dose ablative radiation remedy, was very effectively tolerated, with no grade three or better antagonistic occasions associated to MDT noticed.
The research’s exploratory endpoints aimed to research the results of MDT on the physique’s immune system, following earlier analysis demonstrating its potential to spice up immune response. The researchers discovered that systemic immune activation occasions had been related to MDT and correlated with improved PFS.
“The outcomes counsel that metastasis-directed remedy is efficient and secure for sufferers with oligometastatic pancreatic most cancers,” mentioned principal investigator Chad Tang, M.D., affiliate professor of Radiation Oncology. “However, bigger trials are needed to verify the survival benefit noticed with metastasis-directed native remedy and to research systemic immune activation as a possible mechanism for therapeutic advantages.”
Primarily based on these findings, MD Anderson will lead the Section III EXPAND trial, which is able to open later this yr. The randomized medical trial will take a look at whether or not MDT improves each PFS and total survival for sufferers with oligometastatic pancreatic most cancers. The trial additionally plans to enroll sufferers at MD Anderson and sure MD Anderson Most cancers Community® accomplice websites.
This research was supported by the Most cancers Prevention and Analysis Institute of Texas (CPRIT) (RP180140), the Nationwide Most cancers Institute of the Nationwide Institutes of Well being (P30 CA016672), the Translational Molecular Pathology-Immunoprofiling Laboratory, the Andrew Sabin Household Fellowship, and the Fund for Innovation in Most cancers Informatics. Ludmir and Tang haven’t any conflicts of curiosity to report.
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Journal reference:
Ludmir, E. B., et al. (2024). Addition of Metastasis-Directed Remedy to Systemic Remedy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Section II Trial. Journal of Scientific Oncology. doi.org/10.1200/JCO.24.00081.
