Radiofrequency Ablation and Chemotherapy vs Chemotherapy Only in Locally Advanced Pancreatic Cancer: The PELICAN Randomized Clinical Trial

Abstract

IMPORTANCE: The poor prognosis and limited treatment options in patients with locally advanced pancreatic cancer (LAPC) highlight the need for novel therapies to increase survival. OBJECTIVE: To assess whether the addition of radiofrequency ablation (RFA) to chemotherapy improves survival when compared with chemotherapy only in patients with nonprogressive LAPC. DESIGN, SETTING, AND PARTICIPANTS: This international randomized clinical trial was performed from April 7, 2015, through December 6, 2022, in patients with unresectable LAPC with at least stable disease after 2 months of induction chemotherapy. The predefined study protocol reported a follow-up period of 18 months. Data analysis was performed from February 1, 2024, through January 15, 2025. INTERVENTION: Randomization to receive either RFA with chemotherapy or chemotherapy alone. MAIN OUTCOMES AND MEASURES: Primary outcome was overall survival. Secondary outcomes included progression-free survival, adverse events, and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and pancreatic cancer module. RESULTS: Overall, 188 patients (median [IQR] age, 65 [57-70] years; 100 [53%] men) were randomized, 95 to RFA with chemotherapy and 93 to chemotherapy only. Before randomization, induction chemotherapy had consisted of modified FOLFIRINOX (fluorouracil, oxaliplatin, irinotecan, and leucovorin) in 81 patients (85%) and a gemcitabine-based regimen in 14 patients (15%) in the RFA group vs 80 patients (86%) and 13 patients (14%) in the chemotherapy group, respectively. After a median follow-up of 55 months, median overall survival from randomization was 12.1 months (95% CI, 9.9-14.3 months) in the RFA group vs 11.6 months (95% CI, 9.4-13.9 months) in the chemotherapy group (hazard ratio, 1.07; 95% CI, 0.80-1.45; P = .64). Median progression-free survival was 5.8 months (95% CI, 4.4-7.2 months) in the RFA group and 6.9 months (95% CI, 5.3-8.5 months) in the chemotherapy group (P = .47). Grade 3 or higher serious adverse events were reported more often in the RFA group: 26 patients (27%) vs 10 patients (11%) (P = .004). Mean changes from baseline of -14.6, -12.0, and -18.4 were observed for the Global Health Status quality-of-life scores at 1, 3, and 18 months, respectively, numerically exceeding the threshold of 10 points for clinical relevance. In the chemotherapy-only group, mean changes from baseline on the Global Health Status remained below the threshold for clinical relevance. CONCLUSIONS AND RELEVANCE: This randomized clinical trial of patients with LAPC after 2 months of multiagent chemotherapy found that local ablative therapy with RFA did not improve survival compared with chemotherapy only and adversely affected patient's quality of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03690323.