Chemoimmunotherapy with or without locoregional therapy for biliary tract cancer: A propensity score–matched study.

Abstract

e16185 Background: , Recent phase II studies, including MISPHERE and ABC-07, suggest benefit from combining locoregional therapies such as selective radioembolization with yttrium-90(Y-90) microspheres and external beam radiotherapy with gemcitabine/cisplatin in selected patients with intrahepatic cholangiocarcinoma. However, the benefit of adding locoregional therapy to contemporary chemoimmunotherapy across biliary tract cancer (BTC) subtypes remains unknown. Importantly concurrent locoregional therapy was not permitted in the TOPAZ-1 or KEYNOTE-966. Methods: We conducted a multicenter retrospective cohort study of patients with unresectable or metastatic biliary tract cancer treated with first-line chemoimmunotherapy. Patients were categorized based on receipt of concurrent locoregional therapy at any point during the first-line therapy course including Y-90 radioembolization (Y90-SIRT), external beam radiotherapy (EBRT), transarterial chemoembolization (TACE), or ablation versus chemoimmunotherapy alone. Propensity score (PS) was calculated using logistic regression and PS- matching was performed with 1:1 nearest neighbor for age, gender, Charlson-morbidity index, ECOG status, BTC subtype and tumor burden. Progression free survival and overall survival were assessed using Kaplan–Meier analysis and compared using Cox proportional hazards models. Results: Among 294 patients with advanced BTC, 31 received concurrent locoregional therapy (Y90-SIRT, n = 14; RT, n = 14; TACE, n = 2; ablation, n = 1). Treatment predominantly consisted of gemcitabine-cisplatin and durvalumab (n = 286; 97%). Median follow-up was 18 months. Propensity score matching yielded 62 patients (31 per group), with well-balanced age, gender, Charlson-morbidity index, biliary tract subtype, tumor burden and performance status (standardized mean difference < 0.1). Concurrent locoregional therapy was associated with improved progression-free survival (mPFS, 14.1 vs 7.8 months; HR, 0.45; 95% CI, 0.24-0.87; p = 0.017) and improved overall survival (mOS, 32.0 vs 14.8 months; HR, 0.38; 95% CI, 0.18-0.81; p =0.013) compared to chemoimmunotherapy alone. Results remained consistent in post-matching multivariable Cox models adjusting for biliary tract cancer subtype. Conclusions: In this multicenter propensity score–matched analysis, the addition of locoregional therapy to first-line chemoimmunotherapy was associated with improved progression-free and overall survival in advanced biliary tract cancer. These findings should be interpreted in light of the retrospective design, including the potential for treatment-selection bias, immortal time bias, and residual confounding. Prospective studies are warranted to define the role of concurrent locoregional therapy, with careful attention to patient selection, optimal modality, and timing of treatment intensification.