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

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.