Background Hepatic artery infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC), respectively. However, the combination of the two treatments has not been reported. In this study, we compared the efficacy of HAIC combined with anti-PD-1 immunotherapy (HAICAP) and HAIC in patients with advanced HCC. Methods Between November 2018 and December 2019, advanced HCC patients that were treated with either HAICAP or HAIC were retrospectively recruited and reviewed for eligibility. Efficacy was evaluated according to tumor response and survival. Results As a result, 229 patients were included in this study. Patients were divided into HAICAP group (n = 81) and HAIC group (n = 148) accordingly. The follow-up time ranged from 1.0 to 21.6 months, with a median of 11.0 months. The median overall survival was 18.0 months in the HAICAP group and 14.6 months in the HAIC group (p = 0.018; HR = 0.62; 95% CI 0.34–0.91). The median progression-free survival was 10.0 months in the HAICAP group and 5.6 months in the HAIC group (p = 0.006; HR = 0.65; 95% CI 0.43–0.87). The disease control rate in overall response (83% vs 66%; p = 0.006) and intrahepatic response (85% vs 74%, respectively; p = 0.045) were higher in the HAICAP group than in the HAIC group. Conclusion In comparison to HAIC, HAICAP was associated with a better treatment response and survival benefits for patients with advanced HCC.
Background Inflammatory response is related to cancer progression and patient survival. However, the value in predicting survival in hepatocellular carcinoma (HCC) patients who received anti-PD-1 therapy has not been elucidated. This study aimed to compare the predictive ability of inflammation-based scores for the prognosis of HCC patients after anti-PD-1 therapy. Methods A total of 442 patients who received anti-PD-1 therapy were included in the study. Representative inflammation-based prognostic scores, including the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein (CRP) ratio (LCR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), CRP-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), and prognostic index (PI), were assessed for prediction accuracy using Kaplan–Meier survival curves, time-dependent receiver operating characteristic (ROC) and Harrell’s concordance index (C-index) analyses. Results All the inflammation-based prognostic scores exhibited good discriminatory ability in overall survival (OS) (all P < 0.01), while the PNI score was a unique independent predictor for OS in multivariate analysis (hazard ratio, 1.770; confidence interval, 1.309–2.393; P < 0.001). The areas under the ROC curves at 6, 12, 18 and 24 months and the C-index (0.65) demonstrated that the predictive accuracy of the PNI score was superior to that of the other inflammation-based scores. Conclusion The PNI score is a discriminatory prognostic indicator for OS in HCC patients with anti-PD-1 therapy and is superior to the other inflammation-based prognostic scores in terms of predictive ability.
Background Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy. Methods A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS. Results Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006). Conclusion Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.
Background This study aimed to evaluate the efficiency and prognostic factors of lenvatinib plus programmed death 1 (PD-1) blockades in patients with advanced hepatocellular carcinoma (HCC), especially for those with tumor occupation ≥50% volume of liver (TO ≥50%) or invasion in Vp4, who were excluded from the trial KEYNOTE-524. Methods We reviewed the clinical data of patients with unresectable HCC who received lenvatinib plus PD-1 blockades. The Kaplan-Meier method was performed to compare the progression-free survival (PFS) and the overall survival (OS). Cox proportional hazards model was adopted to identify independent prognostic factors. Results The median PFS and OS of the enrolled 84 HCC patients (31 patients with TO ≥50% and 30 patients with Vp4 invasion) were 6.6 and 11.4 months respectively. TO ≥50% had significantly negative impact on the objective response rates (ORR) (p = 0.015). HCC patients with TO ≥50% had significantly worse PFS and OS than those with TO < 50% (both p value < 0.001). Conversely, invasion in Vp4 did not significantly affect the ORR, PFS or OS for HCC patients receiving lenvatinib plus PD-1 blockades (p = 0.419, 0.528 and 0.855). After multivariate analyses, TO ≥50% was the independent predictor for PFS and OS (both p value < 0.001). No significant correlation was found between any kind of AEs and TO ≥50% or invasion in Vp4. Conclusion Lenvatinib plus PD-1 blockades can provide survival benefits for HCC patients with invasion in Vp4 and the indications of lenvatinib plus pembrolizumab may be further expanded. Locoregional treatments should be considered for patients with TO ≥50% during systemic therapy.
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