Metastasis-directed radiation therapy may be ‘paradigm shift’ in advanced pancreatic cancer
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Key takeaways:
- Researchers observed a more than fourfold improvement in PFS with the addition of metastasis-directed therapy to chemotherapy.
- No grade 3 or greater adverse events occurred in the investigative arm.
The addition of comprehensive metastasis-directed radiation therapy to chemotherapy improved outcomes for patients with oligometastatic pancreatic ductal adenocarcinoma, according to results of a randomized phase 2 basket trial.
Researchers noted a nearly fourfold improvement in PFS with the investigative strategy.
“Patients with metastatic pancreatic cancer have limited treatment options and poor outcomes,” Ethan B. Ludmir, MD, assistant professor of gastrointestinal radiation oncology at The University of Texas MD Anderson Cancer Cener, said in a press release. “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.”
Metastasis-directed therapy uses high-dose ablative radiation to target metastases, with the goal of eliminating cancer cells at all sites. The strategy primarily has been investigated for patients with oligometastatic disease determined by imaging to have five or fewer metastases.
One component of the EXTEND basket trial included 41 patients with oligometastatic pancreatic ductal adenocarcinoma. Researchers assigned them 1:1 to chemotherapy alone or with metastasis-directed radiation therapy.
PFS served as the primary endpoint, with assessments performed after all patients achieved at least 6 months of follow-up. Researchers also evaluated systemic immune response measures as exploratory endpoints.
The analysis included 40 evaluable patients. Study protocol allowed crossover from the control group to the investigative group.
After median follow-up of 17 months, researchers reported longer median PFS among patients assigned metastasis-directed radiation therapy (10.3 months vs. 2.5 months; HR = 0.43; 95% CI, 0.2-0.94).
The investigational approach extended median time to new lesion recurrence (14 months vs. 5 months), and a higher percentage of patients who received metastasis-directed therapy achieved 12-month freedom from new lesion recurrence (54% vs. 38%).
No grade 3 or greater adverse events related to metastasis-directed therapy occurred.
Systemic immune activation events correlated with improved PFS among patients assigned metastasis-directed therapy.
“The results suggest that metastasis-directed therapy is effective and safe for patients with oligometastatic pancreatic cancer,” investigator Chad Tang, MD, associate professor of radiation oncology at MD Anderson, said in the release. “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.”
The phase 3 EXPAND trial — which will assess whether metastasis-directed therapy improves both PFS and OS for patients with oligometastatic pancreatic cancer — is expected to open later this year.
References:
- Ludmir EB, et al. J Clin Oncol. 2024;doi:10.1200.JCO.24.00081.
- The University of Texas MD Anderson Cancer Center. Adding metastasis-directed radiation therapy boosts progression-free survival in metastatic pancreatic cancer (press release). Available at: https://www.mdanderson.org/newsroom/adding-metastasis-directed-radiation-therapy-boosts-progression-free-survival-in-metastatic-pancreatic-cancer.h00-159699912.html. Published Aug. 5, 2024. Accessed Aug. 14, 2024.
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Ludmir EB, et al. J Clin Oncol. 2024;doi:10.1200.JCO.24.00081.
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