Phase I study of proton therapy in adjuvant pancreatic cancer (PROTON-PANC).

Abstract

709 Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 10%. The current standard of care for patients with resectable disease is surgical resection followed by 6 months of adjuvant mFOLFIRINOX (mFFX) chemotherapy. As survival outcomes and distant recurrence rates improve with the use of mFFX, locoregional recurrence remains a significant cause of morbidity and mortality. We sought to integrate short-course proton radiation therapy (PRT) to the operative bed between cycles of adjuvant chemotherapy in patients with resected PDAC of the pancreatic head. Methods: Between 2019 and 2022, patients with resected PDAC with an R0 or R1 resection on adjuvant mFFX were enrolled in a phase I trial using a 3+3 dose-escalation schema (NCT03885284). Patients received mFFX as used in the PRODIGE 24 study and also received short-course PRT delivered over 1 week in 5 fractions (5 GyE each) between cycles 6 and 7 of mFFX. In dose level 1 (DL1), patients received PRT on days 15-19 in a 28-day cycle before starting cycle 7, and in dose level 2 (DL2) patients received PRT on days 8-12 in a 21-day cycle before starting cycle 7. Results: Nine patients were enrolled on the trial, median age 66 (range 52-78). Five had R0 resections, 4 had R1 resections, and 5 had node-positive disease. No patients received preoperative therapy, and none underwent vein reconstruction. Three patients were enrolled on DL1 and 6 patients on DL2. One dose limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed the planned 12 cycles of mFFX (range 7-12, median 11). None of the patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence free. With a median follow up from date of chemotherapy start of 12.5 months, median time to disease recurrence was 12 months (95% confidence interval [CI] 4-not reached [NR]), and median overall survival has not been reached (95% CI 6-NR, 2-year survival rate 57%). Conclusions: PRT integrated within adjuvant mFFX was well-tolerated and no local recurrence was observed for patients with resected PDAC. These findings warrant being confirmed in a phase II trial. Clinical trial information: NCT03885284 .