Results from the AGITG MASTERPLAN trial, presented by Andrew Oar at ESMO 2026 during the Rapid Oral 1 Session: Gastrointestinal Tumours, Upper Digestive, showed that adding stereotactic body radiotherapy (SBRT) to chemotherapy significantly reduced locoregional recurrence and improved progression-free survival in patients with high-risk operable, borderline resectable, or locally advanced pancreatic cancer.
The randomized study also reported a promising overall survival benefit, with median survival increasing from 14 to 22 months, without a statistically significant increase in grade 3 or higher toxicity.
Background
Despite advances in systemic chemotherapy, locoregional recurrence remains a major challenge in pancreatic cancer, contributing to disease-related complications and mortality.
Stereotactic body radiotherapy delivers high doses of radiation with high precision over a limited number of treatment sessions, potentially improving local disease control while minimizing exposure to surrounding healthy tissues.
The AGITG MASTERPLAN trial investigated whether adding SBRT to contemporary chemotherapy could improve outcomes in patients with pancreatic cancer, including those with high-risk operable, borderline resectable, and locally advanced disease.
Study Design and Patient Population
The study enrolled 75 patients across 14 participating centers, with 74 eligible for analysis.
Patients were classified into two groups based on resectability:
- Potentially operable pancreatic cancer (POPC): Patients with borderline resectable disease or operable tumors with at least one high-risk feature, including tumor size greater than 4 cm, extrapancreatic extension, or lymph node involvement.
- Inoperable pancreatic cancer (IPC): Patients with locally advanced or medically inoperable disease.
Of the 74 eligible patients, 48 had potentially operable disease and 26 had inoperable disease. Participants were randomized 2:1 to receive three months of chemotherapy plus SBRT or chemotherapy alone. Chemotherapy consisted of modified FOLFIRINOX or gemcitabine plus nab-paclitaxel, selected by the treating clinician.
Patients assigned to the experimental arm received SBRT at 40 Gy in five fractions, with fiducial marker guidance and real-time radiotherapy quality assurance.
Following initial treatment, patients were reassessed for surgery. Those undergoing resection received an additional three months of adjuvant chemotherapy, while patients who were not suitable for surgery continued systemic chemotherapy for another three months.
The primary endpoint was locoregional recurrence at 12 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), surgical outcomes, and toxicity.
Locoregional Recurrence Results
The addition of SBRT significantly reduced the risk of locoregional recurrence. At 12 months, locoregional recurrence was 20.2% with chemotherapy plus SBRT compared with 52.0% with chemotherapy alone (P=0.022).
The benefit was particularly evident in patients with potentially operable disease:
- Chemotherapy plus SBRT: 19.7% locoregional recurrence.
- Chemotherapy alone: 52.9%.
- P=0.031.
Among patients with inoperable disease, 12-month locoregional recurrence was 21.4% with SBRT versus 50.0% with chemotherapy alone. However, this difference was not statistically significant (P=0.16).
These findings suggest that SBRT may meaningfully improve locoregional disease control when incorporated into multimodality treatment.
Progression-Free and Overall Survival
In addition to improved local control, the experimental treatment arm demonstrated significantly longer progression-free and overall survival. Median progression-free survival was 11.9 months with chemotherapy plus SBRT versus 6.3 months with chemotherapy alone (P=0.002).
A notable overall survival difference was also observed:
Median overall survival reached 22.0 months with SBRT compared with 14.0 months in the chemotherapy-only group (P=0.006).
The eight-month difference in median overall survival represents an encouraging finding, although the relatively small study population means that these results require confirmation in larger trials.
Surgical Outcomes
Among the 48 patients with potentially operable pancreatic cancer, 31 were assigned to chemotherapy plus SBRT and 17 to chemotherapy alone.
Surgical resection was performed in:
- 21 of 31 patients (68%) in the SBRT group.
- 10 of 17 patients (59%) in the chemotherapy-alone group.
The difference was not statistically significant (P=0.54).
Among patients undergoing surgery, an R0 resection, defined as a margin greater than 1 mm, was achieved in 62% versus 40%, respectively (P=0.44). Although numerically favorable, these differences were not statistically significant.
Safety Findings
The addition of SBRT did not result in a statistically significant increase in severe adverse events. Grade 3 or higher toxicity occurred in 70.2% of patients receiving chemotherapy plus SBRT versus 64.0% receiving chemotherapy alone (P=0.27).
Investigators concluded that the addition of SBRT improved locoregional control and progression-free survival without a demonstrated increase in overall severe toxicity. , 39 of 49 patients (80%) assigned to the experimental arm initiated SBRT, which should be considered when interpreting the findings.
Clinical Implications
The AGITG MASTERPLAN results provide encouraging evidence supporting further investigation of SBRT as part of multimodality treatment for pancreatic cancer. The reduction in locoregional recurrence from 52.0% to 20.2% at 12 months is particularly relevant given the morbidity associated with uncontrolled local disease.
Improvements in progression-free survival and the observed overall survival signal further strengthen the rationale for investigating SBRT alongside modern chemotherapy regimens.
However, the study included a relatively small and heterogeneous population, encompassing potentially operable and inoperable pancreatic cancer. Larger randomized trials are needed to confirm the survival findings, determine which patients benefit most, and establish the optimal integration of SBRT with systemic therapy and surgery.
Conclusion
The AGITG MASTERPLAN trial showed that adding SBRT at 40 Gy in five fractions to chemotherapy significantly improved 12-month locoregional control and progression-free survival in patients with high-risk operable, borderline resectable, or locally advanced pancreatic cancer.
The study also demonstrated a promising overall survival difference of 22 versus 14 months, without a statistically significant increase in grade 3 or higher toxicity.
These results support further evaluation of SBRT as part of multidisciplinary pancreatic cancer treatment, particularly to improve local disease control and potentially extend survival.
