A single-center experience of chemotherapy combined with radiofrequency ablation and immunotherapy in patients with locally advanced/metastatic pancreatic ductal adenocarcinoma.

Abstract

e16413 Background: Standard of care (SOC) chemotherapy with either FOLFIRINOX or gemcitabine/nab-paclitaxel provides an overall response rate (ORR) < 35% in locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). In preclinical and clinical publications, we previously reported that radiofrequency ablation (RFA) decreases tumor size and potentiates anti-tumor immunity. Additionally, we reported that the combination of RFA and PD-L1 inhibitor sustained anti-tumor immunity and had a greater efficacy to reduce tumor size in treated and distant tumors than RFA alone. Based on these studies, we hypothesized that trimodal therapy with chemotherapy, RFA, and immunotherapy in patients with unresectable and metastatic PDAC may synergistically improve ORR. Methods: At our center, patients with newly diagnosed locally advanced or metastatic PDAC were treated with SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) and endoscopic ultrasound-guided RFA (EUS-RFA) of the primary pancreatic tumor. Fourteen patients received pembrolizumab via compassionate care use. Patients were given 6 weeks of chemotherapy followed by EUS-RFA every 6 weeks until tumor had complete response. Pembrolizumab was administered after each EUS-RFA session and continued every 6 weeks concurrent with chemotherapy. Primary endpoint was ORR and secondary endpoints were progression free survival (PFS) and overall survival (OS). Results: In our cohort of 14 patients, 6 patients (43%) were locally advanced PDAC (LAPC) and 8 patients (57%) had metastatic disease. Median age was 64.5 (range, 49-83 years) with 10 (71%) females and 4 males. Four patients (29%) had a CDKN2A somatic mutation, and 6 patients had CA 19-9 > 500. One patient with LAPC downstaged to resectable disease and underwent a successful Whipple surgery. Three metastatic patients (21%) had progression of disease with a median PFS of 11.5 months. The ORR (based on ultrasound-guided imaging during EUS-RFA) is 93% (13/14 patients) with median tumor shrinkage of 54% and median CA 19-9 decrease of 41%. Radiographic responses on EUS peaks after the 5th RFA treatment. Six patients (43%) who completed the 5th EUS-RFA had a smaller tumor burden on imaging studies. One patient (16%) had a complete response based on EUS, while 5 (83%) patients had more than 50% shrinkage of tumor size. Conclusions: SOC chemotherapy in combination with EUS-RFA, followed by immunotherapy was highly effective in disease control in locally advanced/metastatic PDAC and potentially prolongs PFS, compared to historical controls who received chemotherapy alone.