Adjuvant hepatic arterial infusion pump chemotherapy with floxuridine for patients with resectable colorectal liver metastases and a low clinical risk score: A randomized controlled trial—The PUMP trial.

Abstract

LBA3506 Background: Recurrence after local treatment for colorectal liver metastases (CLM) occurs in up to 70% of patients, frequently confined to the liver. Dutch guidelines do not recommend adjuvant chemotherapy, because three randomized controlled trials (RCTs) have shown no overall survival (OS) benefit of perioperative systemic chemotherapy in resectable CLM. Hepatic arterial infusion pump (HAIP) chemotherapy delivers high doses of floxuridine directly to the liver. This trial evaluated the effectiveness of adjuvant HAIP chemotherapy with floxuridine compared to resection alone in patients with resectable CLM and a low clinical risk score (CRS). Methods: This is an open-label, investigator-initiated, multicenter, randomized phase III trial. Adult patients with resectable CLM, no extrahepatic disease, and CRS 0–2 were randomized 1:1 to resection plus adjuvant HAIP chemotherapy with floxuridine versus resection alone, both without adjuvant systemic chemotherapy. Preoperative systemic chemotherapy prior to randomization was allowed. Patients in both groups who signed informed consent but did not fulfill inclusion criteria at the time of surgery were excluded and replaced. Patients were scheduled for 6 cycles of HAIP chemotherapy with floxuridine (0.12 mg/kg/day) that was initiated 4–12 weeks after placement of a Tricumed constant flow pump. The primary endpoint was progression-free survival (PFS) calculated from the date of surgery to the date of a recurrence or death. Secondary endpoints included hepatic PFS (hPFS) and ninety-day mortality. Survival was estimated using Kaplan-Meier method and compared using a log-rank test. Results: Between August 2018 and March 2026, 243 patients were randomized to resection followed by adjuvant HAIP (n=120) or resection alone (n=123). At time of surgery, 25 patients were excluded due to presence of extrahepatic disease, unresectable CLM or histopathological confirmation of benign disease. In this analyses, 110 patients were included in the resection and adjuvant HAIP group and 108 patients in the resection alone group. In the HAIP group, 100 patients (91%) initiated HAIP chemotherapy, and the median number of administered cycles was 5 [IQR 3-6]. Treatment was discontinued in 8 patients (8%) due to recurrence and in 32 patients (32%) due to toxicity. The median PFS was 15.0 months in HAIP group vs 16.0 months in resection alone group (HR 0.88; 95% CI 0.62–1.25; p=0.48). The median hPFS was 37.6 months in HAIP group vs 21.8 months in resection alone group (HR 0.80; 95% CI 0.54–1.17; p=0.25). Ninety-day postoperative mortality was observed in 4 patients (3.3%) in the HAIP group and in 1 patient (0.8%) after resection alone. No mortality was attributed to pump placement or HAIP chemotherapy. Conclusion: In patients with resectable CLM and a low CRS, no improvement in PFS after adjuvant HAIP chemotherapy with floxuridine compared to resection alone could be demonstrated. Mature results for overall survival are expected in 2029. EudraCT number: 2018-001696-21. Clinical trial information: 2018-001696-21.