Radiotherapy with Combination Therapy of Immune Checkpoint Inhibitors and Anti-Angiogenic Therapy for Hepatocellular Carcinoma
Menée à l'aide de données portant sur 76 patients atteints d'un carcinome hépatocellulaire de stade avancé traité par inhibiteurs de points de contrôle immunitaire combinés à une thérapie anti-angiogénique (durée médiane de suivi : 15,5 mois), cette étude évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la sécurité de l'ajout d'une radiothérapie au traitement
Purpose: Immune checkpoint inhibitors (ICIs) combined with anti-angiogenic therapy have limited efficacy in treating advanced hepatocellular carcinoma (HCC). The synergistic effect from the systemic therapy and radiotherapy (RT) might resolve this problem. We aimed to investigate the effect of RT on the treatment outcomes of ICIs and anti-angiogenic combination therapy in patients with advanced-stage HCC. Methods and Materials: This retrospective observational study analyzed the medical records of 194 patients with Barcelona Clinic Liver Cancer stage C HCC who were admitted to our center from August 2018 to June 2022 and received ICIs combined with anti-angiogenic therapy as the first-line treatment. Patients who were administered RT for tumor thrombus or symptomatic metastases within 8 weeks of the commencement of combination therapy were allocated to the RT group, while those who did not receive radiotherapy were assigned to the non-radiotherapy (NRT) group. Propensity score matching (PSM) was utilized to mitigate the selection bias. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), local PFS (LPFS), out-of-field PFS (OutPFS), and treatment-related adverse events (TRAEs). Results: A total of 76 patients diagnosed with advanced-stage HCC and treated with ICIs and anti-angiogenic therapy were included in the study, with 33 patients in the RT group and 43 patients in the non-RT group. After PSM, 29 matched patient pairs were generated. The median follow-up was 15.5 months, and the RT sites were mainly located on the tumor thrombus (55.2%) and extrahepatic metastatic lesions (48.3%). The median PFS was 8.3 months (95% confidence interval (CI): 5.4–11.3) in the RT group and 4.2 months (95% CI: 3.4–5.0) in the NRT group (p<0.001). The median OS was not reached in the RT group and 9.7 months (95% CI: 4.1–15.3) in the NRT group (p=0.002). The ORR was 75.9% (95% CI: 56.5–89.7) in the RT group and 24.1% (95% CI: 10.3–43.5) in the NRT group (p<0.001). The DCR was 100% in the RT group and 75.9% (95% CI: 56.5–89.7) in the NRT group (p=0.005). The median LPFS and OutPFS was 13.2 months (95% CI: 6.3–20.1) and 10.8 months (95% CI: 7.0–14.7), respectively. RT was an independent prognostic factor for PFS (HR=0.33; 95% CI: 0.17–0.64; p <0.001) and OS (HR=0.28; 95% CI: 0.11–0.68; p=0.005), respectively. The rates of any grade TRAEs were similar between the two groups. Conclusions: In comparison to the combination of ICIs and anti-angiogenic therapy, the inclusion of RT has been observed to improve the DCR and survival outcomes in patients with advanced-stage HCC. The safety profile of this triple therapy was satisfactory.
International Journal of Radiation Oncology, Biology, Physics