Tislelizumab and hypofractionated radiotherapy plus nab-paclitaxel/gemcitabine as conversion therapy for BRPC/LAPC: A Phase II trial with dynamic biomarker monitoring
Mené sur 56 patients atteints d'un cancer du pancréas à la limite de la résécabilité ou localement avancé, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, du tislélizumab en combinaison avec une chimioradiothérapie hypofractionnée par nab-paclitaxel/gemcitabine
Purpose: The optimal conversion treatment for patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer (BRPC/LAPC) remains unclear. Here we present the efficacy and safety results of a phase II trial evaluating tislelizumab combined with hypofractionated radiotherapy plus nab-paclitaxel/gemcitabine (THAG) in BRPC/LAPC patients (ChiCTR2000032955, NCT05634564).
Patients and Methods: This phase II trial enrolled 56 BRPC/LAPC patients (BRPC: 17, 30.4%; LAPC: 39, 69.6%). Participants received tislelizumab plus AG (nab-paclitaxel/gemcitabine) in 21-day cycles. Non-progressing patients received concurrent radiotherapy during the third chemotherapy cycle. After four treatment cycles, a multidisciplinary team (MDT) assessed eligibility for radical surgery. Dynamic biomolecular profiling was performed.
Results: Fifty-six eligible patients were enrolled. The objective response rate (ORR) was 51.8% (95% CI 38.0-65.3%). Median progression-free survival (mPFS) was 13.2 months (95% CI 11.6–19.4 months) and median overall survival (mOS) was 21.3 months (95% CI 18.8-not reached [NR]). Among 30 patients who reached criteria for surgical resectability, 22 patients (22/56, 39.3%) underwent radical resection, comprising 9 BRPC patients (9/17, 52.9%) and 13 LAPC patients (13/39, 33.3%). The R0 resection rate reached 90.9% (95% CI 70.8-98.9%), and the mOS of patients who underwent surgery was 34.0 months (95%CI 20.1-NR). Grade ≥3 adverse events (AEs) occurred in 33/56 patients (58.9%). Dynamic biomarker exploration revealed that baseline IL-6 level (>5 pg/ml) predicted better PFS. Moreover, ctDNA status and clearance demonstrated superior survival.
Conclusions: The THAG regimen as preoperative therapy showed encouraging clinical activity with a manageable safety profile. Dynamic biomarker findings reveal potential for guiding precision treatment strategies with THAG.
Clinical Cancer Research , résumé, 2025