Abstract C004: A window-of-opportunity trial using neoadjuvant hepatic artery chemotherapy for patients with localized pancreas cancer: Interim analysis of safety and feasibility
Authors: Agritelley Ethan S , Kanu Elishama N , Bao Jiayin , Fletcher Ashley A , Skinner Holly , Molvin Adi , Murray Stacy , Kim Charles Y , Cline Brendan , Mastria Eric , Johnson David Y , DeVito Nicholas C , Blobe Gerard C , Abbruzzese James L , Crosby Erika J , Martin Allison , Mettu Niharika B , Allen Peter J , Nussbaum Daniel P 
Published: September 2024

Abstract
Less than 20% of patients diagnosed with pancreatic cancer will present with localized disease and receive both resection and systemic therapy. Within this group of patients, actual 10-year survival is approximately 5%. The liver is the most common site of recurrent disease and is associated with the worst survival outcomes. Randomized trials in patients with localized colorectal cancer have shown the addition of single-dose, neoadjuvant hepatic artery (HA) chemotherapy, which administers a high-dose of chemotherapy directly to the liver, improves liver metastasis-free and overall survival. Because PDAC and colorectal cancer have similar recurrence patterns and are treated with similar systemic therapy, we hypothesized this strategy could improve recurrence rates and potentially overall survival in patients with localized PDAC. This is a prospective, non-randomized window-of-opportunity trial testing single-dose neoadjuvant HA chemotherapy in patients with resectable or borderline resectable PDAC. Target enrollment is 20 patients treated in two arms: three months of mFOLFIRINOX before surgery and three months after, or upfront surgery followed by six months of mFOLFIRINOX. In both arms, patients undergo diagnostic laparoscopy and percutaneous delivery of the experimental HA therapy (floxuridine and oxaliplatin) one week before surgery. Patients then undergo resection of their primary tumor, followed by short-term follow-up, where safety evaluations are performed for 30 days. Patients then enter long-term follow-up, where efficacy will be assessed every three months for up to three years. The primary endpoint is safety and feasibility. Secondary endpoints include three-year disease-free, liver metastasis-free, and overall survival. To date, eight patients have been screened and seven enrolled: four in the neoadjuvant therapy arm and three in the upfront resection arm. All patients have completed the treatment period and 86% have completed short-term follow-up. Mean age was 63+/-11 years and 57% were female. Mean CA 19-9 prior to resection was 60.3+/-50 U/mL. Conventional hepatic artery anatomy was present in 57% of patients. HA chemotherapy was delivered through the proper hepatic artery in 86% of patients, and via the left and right hepatic arteries in 14%. Concomitant ligation or embolization of accessory hepatic arteries was required in 43%. The mean tumor size was 2.5+/-0.8 cm and lymph node metastases were present in 86%; three patients had a microscopically positive resection margin. Four of the seven patients experienced adverse events, including one grade 2 event, three grade 3 events, and one grade 4 event. However, none were attributed to the experimental therapy. At this interim analysis, single-dose neoadjuvant HA chemotherapy appears to be feasible and safe in patients undergoing resection of localized PDAC. We anticipate enrollment to be completed within the calendar year. Long- term follow-up will be required to resolve survival outcomes and correlative endpoints.
Citation Format: Ethan S Agritelley, Elishama N Kanu, Jiayin Bao, Ashley A Fletcher, Holly Skinner, Adi Molvin, Stacy Murray, Charles Y Kim, Brendan Cline, Eric Mastria, David Y Johnson, Nicholas C DeVito, Gerard C Blobe, James L Abbruzzese, Erika J Crosby, Allison Martin, Niharika B Mettu, Peter J Allen, Daniel P Nussbaum. A window-of-opportunity trial using neoadjuvant hepatic artery chemotherapy for patients with localized pancreas cancer: Interim analysis of safety and feasibility [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C004.