Effect of different PD‐1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma

Abstract

SummaryBackgroundImmune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC).AimTo compare the effect of different anti‐PD‐1 combination therapies as the first‐line treatments for uICC.MethodsThis study included 318 patients who received chemotherapy alone (Chemo), anti‐PD‐1 plus chemotherapy (ICI‐chemo), anti‐PD‐1 plus targeted therapy (ICI‐target) or anti‐PD‐1 plus targeted therapy and chemotherapy (ICI‐target‐chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety.ResultsPatients with ICI‐chemo (median PFS [mPFS], 6.3 months; HR: 0.61, 95% CI: 0.42–0.88; p = 0.008; median OS [mOS], 10.7 months; HR: 0.61, 95% CI: 0.39–0.94; p = 0.026), ICI‐target (7.2 months; HR: 0.54, 95% CI: 0.36–0.80; p = 0.002; 15.8 months; HR: 0.54, 95% CI: 0.35–0.84; p = 0.006) or ICI‐target‐chemo (6.9 months; HR: 0.65, 95% CI: 0.47–0.90; p = 0.009; 14.4 months; HR: 0.47, 95% CI: 0.31–0.70; p < 0.001) achieved better clinical outcomes than those with Chemo (3.8 months; 9.3 months). ICI‐target was not inferior to ICI‐chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55–1.42; p = 0.614; HR for OS: 0.89, 95% CI: 0.51–1.55; p = 0.680). ICI‐target‐chemo yielded similar prognoses as ICI‐chemo (HR for PFS: 1.07, 95% CI: 0.70–1.62; p = 0.764; HR for OS: 0.77, 95% CI: 0.45–1.31; p = 0.328) and ICI‐target (HR for PFS: 1.20, 95% CI: 0.77–1.88; p = 0.413; HR for OS: 0.86, 95% CI: 0.51–1.47; p = 0.583) but resulted in more adverse events (p < 0.001; p = 0.010). Multivariable and propensity score analyses supported these findings.ConclusionsAmong patients with uICC, ICI‐chemo or ICI‐target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI‐target‐chemo.

Clinical outcomes of immune checkpoint inhibitor combined with other targeted or immunological therapy regimens for the treatment of advanced bile tract cancer: a systematic review and meta-analysis

“…All the studies, except that of Lei et al. ( 19 ), reported tumor responses (n = 535). Overall, only 3 patients (0.6%) achieved a complete response (CR), while 182 (34.0%) achieved a partial response (PR), and 230 patients (43.0%) had a stable disease (SD) state.…”

“…Among the 15 included studies, there were 5 prospective studies (no randomized controlled trial) (16-18, 24, 25) and 10 retrospective studies (19)(20)(21)(22)(23)(26)(27)(28)(29)(30). All the studies underwent quality appraisal according to the NOS (Supplementary Table 1), with 13 ranked as medium quality, and 2 as high quality.…”

The fibrosis-4 index is a prognostic factor for cholangiocarcinoma patients who received immunotherapy

“…Studies on the application of pembrolizumab for incurable cholangiocarcinoma in Phase I b and II trials have found that regardless of PD-L1 expression, it can effectively control 6%-13% of advanced bile duct cancers, with manageable toxicity (6).A real-world study based on Phase III clinical trial TOPAZ-1, incorporating durvalumab into the first-line chemotherapy regimen for cholangiocarcinoma, demonstrated a 20% reduction in the risk of death (HR=0.80, 95% CI: 0.66-0.97, P=0.021), confirming the efficacy and safety of durvalumab for cholangiocarcinoma patients (7). Subsequently, more studies and case reports on the application of other immune checkpoint inhibitors in cholangiocarcinoma have emerged, further bolstering the case for immunotherapy in cholangiocarcinoma (8)(9)(10)(11).Currently, the combination of durvalumab with gemcitabine and cisplatin is an option for first-line treatment of locally advanced or metastatic cholangiocarcinoma. However, further research is needed to verify the application of immune checkpoint inhibitors in cholangiocarcinoma and to identify prognostic risk factors for patients receiving immunotherapy.…”

Editorial: Advances in immunotherapy and combination therapy for biliary tract cancers

“…Finally, over the past few years, advances in precision oncology have driven the development of immuno- and targeted therapies, changing the paradigm of cancer treatment, including BTC, from a population-based perspective to individualised treatment for each patient and tumour. On this basis, enabling translational surgery for unresectable BTC, thereby further enhancing the survival of BTC patients is also a future concern ( 5 ). Although immunotherapy offers great potential for BTC, there are still a majority of patients who still fail to respond well after treatment.…”