4.7 Article

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

Journal

ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Volume 58, Issue 6, Pages 611-622

Publisher

WILEY
DOI: 10.1111/apt.17623

Keywords

chemotherapy; combination therapy; immune checkpoint inhibitor; immunotherapy; intrahepatic cholangiocarcinoma

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This study compared the efficacy of different anti-PD-1 combination therapies as the first-line treatment for uICC. The results showed that ICI-chemo and ICI-target therapies had better survival outcomes and fewer adverse events compared to chemotherapy. ICI-target-chemo had similar efficacy to ICI-chemo but resulted in more adverse events.
Background: Immune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC).Aim: To compare the effect of different anti-PD-1 combination therapies as the first-line treatments for uICC.Methods: This 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.Results: Patients 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.Conclusions: Among 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.

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