Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial. (March 2023) - Issels, Rolf D.
Abstract: Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma. Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m 2 on day 1, 15 and cisplatin 25 mg/m 2 with RHT on day 2, 3 and 15, 16) or to G (gemcitabine 1000 mg/m 2 on day 1, 8, 15), four-weekly over six cycles. Disease-free survival (DFS) was the primary end-point. Secondary end-points included overall survival (OS) and safety. Results: A total of 117 eligible patients (median age, 63 years) were randomly allocated to treatment (57 GPH; 60 G). With a follow-up time of 56.6 months, the median DFS was 12.7 compared to 11.2 months for GPH and G, respectively (p = 0.394). Median post-recurrence survival was significantly prolonged in the GPH-group (15.3 versus 9.8 months; p = 0.031). Median OS reached 33.2 versus 25.2 months (p = 0.099) with 5-year survival rates of 28.4% versus 18.7%. Excluding eight patients who received additional capecitabine in the G-arm (investigators choice), median OS favoured GPH (p = 0.052). Adverse events CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 occurred in 61.5% (GPH) versus 63.6% (G) of patients. Two patients in the G-group died because of treatment-related toxic effects. Conclusions: The randomised controlled Hyperthermia European Adjuvant Trial study failed to demonstrate a significant difference in DFS. However, it suggests a difference in post-recurrence survival and a trend for improved OS. ClinicalTrials: gov, number NCT01077427. Highlights: First study in PDAC investigating hyperthermia added to adjuvant chemotherapy. The study failed to improve disease-free survival as the primary endpoint. Post-recurrence survival was improved with a trend of improved overall survival. Toxicity compares favorably with a more intensive adjuvant chemotherapy. The study offers new perspectives to gain perioperative benefit in PDAC.