Researchers have demonstrated that adding metastasis-directed radiation therapy to standard-of-care chemotherapy may improve progression-free survival in patients with oligometastatic pancreatic cancer, according to a recent study published by Ludmir et al in the Journal of Clinical Oncology and previously presented at the 2024 ASCO Gastrointestinal Cancers Symposium (Abstract 603).
Background
Metastatic pancreatic cancer spreads rapidly to vital organs, posing significant challenges for disease management. Diagnosis often occurs at an advanced stage, reducing treatment efficacy and decreasing survival rates. The disease’s complexity and resistance to many therapies may also contribute to its poor prognosis. Chemotherapy, the main treatment option, generally offers an average 7-month progression-free survival.
“Patients with metastatic pancreatic cancer have limited treatment options and poor outcomes,” stressed lead study author Ethan Ludmir, MD, Assistant Professor of Gastrointestinal Radiation Oncology at The University of Texas MD Anderson Cancer Center.
Metastasis-directed radiation therapy targets metastases with high-dose ablative radiation therapy, aiming to eliminate all cancer cells at all sites identified on a scan. This approach is primarily being evaluated for patients with oligometastatic disease—an intermediate stage of cancer between a localized tumor and widespread cancer—for whom imaging shows up to five metastases. Metastasis-directed radiation therapy has emerged as a major area of research after a successful initial study in 2016 demonstrated its effectiveness in patients with lung cancer. It has since been shown to be effective in multiple cancer types, including prostate and kidney cancers.
Study Methods and Results
In the multicenter phase II EXTEND trial (ClinicalTrials.gov identifier NCT03599765), the researchers randomly assigned 40 patients with oligometastatic pancreatic cancer to receive either metastasis-directed radiation therapy plus chemotherapy or chemotherapy alone between 2019 and 2023.
The median time to new lesion recurrence was 14 months with metastasis-directed radiation therapy plus chemotherapy vs 5 months with chemotherapy alone. The 12-month freedom from new lesion recurrence rate was 54% among the patients who received metastasis-directed radiation therapy plus chemotherapy and 38% among those who received chemotherapy alone.
After a median follow-up of 17.3 months, the researchers found that progression-free survival was 10.3 months in the patients who received metastasis-directed radiation therapy plus chemotherapy compared with 2.5 months among those who received standard chemotherapy alone. Additionally, increased immune responses from metastasis-directed radiation therapy were found to be connected to longer survival times.
Crossover from chemotherapy alone to metastasis-directed radiation therapy plus chemotherapy was allowed. The researchers reported that metastasis-directed radiation therapy was reported to be well tolerated, with no grade 3 or higher adverse events related to the treatment observed.
The trial’s exploratory endpoints aimed to investigate the effects of metastasis-directed radiation thetapy on the body’s immune system following earlier research demonstrating its potential to boost immune response. The researchers found that systemic immune activation events were associated with the therapy and correlated with improved progression-free survival.
Conclusions
“We are excited to see that the addition of targeted radiation therapy quadrupled the average progression-free survival time, suggesting this approach potentially represents a paradigm shift in treating metastatic pancreatic cancer,” Dr. Ludmir highlighted.
“The results suggest that metastasis-directed [radiation] therapy is effective and safe for patients with oligometastatic pancreatic cancer,” emphasized senior study author Chad Tang, MD, Associate Professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center. “Nevertheless, larger trials are necessary to confirm the survival advantage observed with metastasis-directed local treatment and to investigate systemic immune activation as a potential mechanism for therapeutic benefits,” he underscored.
The researchers plan to lead a phase III EXPAND trial, which will open later in 2024. The randomized clinical trial will test whether metastasis-directed radiation therapy can improve both progression-free and overall survival in patients with oligometastatic pancreatic cancer.
Disclosure: The research in this trial was supported by the Cancer Prevention and Research Institute of Texas, the National Cancer Institute of the National Institutes of Health, the Translational Molecular Pathology–Immunoprofiling Laboratory, the Andrew Sabin Family Fellowship, and the Fund for Innovation in Cancer Informatics. For full disclosures of the study authors, visit ascopubs.org and meetings.asco.org.
