The Role of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review and Pooled Analysis of 2,402 patients
A partir d'une revue systématique de la littérature (63 articles, 2 402 patients), cette étude évalue l'efficacité, du point de vue du taux de réponse objective globale, du taux de contrôle de la maladie, de la survie globale, et la toxicité de diverses immunothérapies chez des patients atteints d'un carcinome hépatocellulaire
Background : Immune checkpoints inhibitors (ICIs) have emerged as a treatment option for several malignancies. Nivolumab, pembrolizumab, nivolumab plus ipilimumab, and atezolizumab plus bevacizumab have been approved for the management of advanced‐stage hepatocellular carcinoma (HCC). We aimed to systematically review the literature and summarize the characteristics and outcomes on HCC patients treated with ICIs. Methods : A systematic literature search of PubMed, the Cochrane Library, and ClinicalTrials.gov was performed according to the PRISMA statement (end‐of‐search date: November 7th, 2020). Quality of evidence assessment was also performed. Results : Sixty‐three articles including 2,402 patients were analyzed, 2,376 of whom received ICIs for unresectable HCC. Response to ICIs could be evaluated in 2,116 patients, and the overall objective response rate (ORR) and disease‐control rate (DCR) were 22.7% and 60.7%, respectively, and the mean overall survival (OS) was 15.8 months. The ORR, DCR and OS for nivolumab (n=846) were 19.7%, 51.1% and 18.7 months, respectively, and for pembrolizumab (n=435) were 20.7%, 64.6% and 13.3 months, respectively. The combination of atezolizumab/bevacizumab (n=460) demonstrated an ORR and DCR of 30% and 77%, respectively. The overall rate of treatment discontinuation due to adverse events was 14.9%. Fifteen patients received ICIs in the liver transplant (LT) setting (one pre‐LT for bridging, 14 for post‐LT recurrence); fatal graft rejection was reported in 40.0% (n=6/15) and mortality in 80.0% (n=12/15). Conclusion : ICIs are safe and effective against unresectable HCC, but caution is warranted regarding their use in the LT setting due to the high graft rejection rate. Implications for Practice : Our systematic review pooled the outcomes from studies reporting on the use of immune checkpoint inhibitors (ICIs) for the management of 2,402 patients with advanced‐stage hepatocellular carcinoma (HCC), 2,376 of whom had unresectable HCC. The objective response rate and disease‐control rate were 22.7% and 60.7%, respectively, and the mean overall survival was 15.8 months. The overall rate of treatment discontinuation due to adverse events was 14.9%. Fifteen patients received ICIs in the liver transplant (LT) setting (one pre‐LT for bridging, 14 for post‐LT recurrence). Six of the them experienced graft rejection (40.0%).
The Oncologist 2020