e16272 Background: Locally advanced, initially unresectable gallbladder cancer (GBC) is associated with a poor prognosis. Although immunotherapy combined with chemotherapy is recommended by NCCN guidelines, its potential to enable conversion surgery remains underexplored. This study evaluated the efficacy and safety of an intensified regimen combining PD-1/PD-L1 inhibitors with gemcitabine-based chemotherapy. Methods: This single-center real-world retrospective study enrolled 47 patients with locally advanced, initially unresectable GBC treated between February 2021 and July 2025, with follow-up through December 31, 2025. The cohort comprised 33 females (70.2%) and 14 males (29.8%). Baseline unresectability was confirmed by a multidisciplinary team (MDT) for all patients. All patients received at least two cycles of immunochemotherapy consisting of PD-1 or PD-L1 inhibitor combined with gemcitabine-based regimens including GAP (n = 32), AG (n = 5), GC (n = 4), GS (n = 3), GEMOX (n = 2), and GCS (n = 1). The primary endpoint was the conversion to surgical resection rate. Secondary endpoints included objective response rate (ORR), R0 resection rate, tumor regression grade (TRG), treatment-related adverse events (TRAEs), and survival outcomes. Results: Patients received a median of 2 conversion therapy cycles (range, 2-10) and were followed up for a median of 15.8 months (range, 4-46 months). 40.4% of patients (19/47) achieved conversion to surgical resection, with an R0 resection rate of 94.7% (18/19). Immunochemotherapy resulted in a median progression-free survival (PFS) of 14.5 months (1-year rate 51.2%, 2-year rate 30.9%) and median overall survival (OS) of 17.3 months (1-year rate 68.6%, 2-year rate 39.4%). The objective response rate (ORR) was 46.8% (22/47), including 1 complete response (CR), 21 partial responses (PR), 15 stable disease (SD), and 10 progressive disease (PD). Surgical patients demonstrated a significant survival benefit compared with non-surgical patients, with superior median OS not reached (NR) vs. 11.4 months, P < 0.001 and PFS (NR vs. 6.4 months, P < 0.001). In the surgical cohort, a major pathologic response (TRG 0-1) was observed in 15.7% (3/19) of surgical patients. Two patients experienced Clavien-Dindo grade ≥3 postoperative complications, with no postoperative deaths. Grade 3-4 TRAEs occurred in 48.9% (23/47) of all patients, with similar incidence between surgical and non-surgical cohorts. Conclusions: The intensified multi-agent immunochemotherapy regimen demonstrated encouraging survival outcomes and manageable toxicity as conversion therapy for initially unresectable locally advanced GBC, supporting its potential as a therapeutic strategy.
Li et al. (Thu,) studied this question.