Better clinical outcomes with Immune checkpoint inhibitors than the standard of care for unresectable HCC

January 2022 Clinical Practice Nalinee Pathak

Meta-analysis of clinical trials suggests that Immune checkpoint inhibitors (ICIs) may be more effective than the standard of care for patients with hepatocellular carcinoma (HCC). This idea is supported by a recent study published in the JAMA network open. This study compares the efficacy of  ICIs vs standard of care by analysing data from three phase 3, randomised clinical trials (RCT): KEYNOTE-240, CheckMate-459, and IMbrave150; summing 1657 patients in total.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant neoplasms, ranking as the fourth most common cause of cancer-related death in the world. Since 2008, sorafenib has been the standard of care for these cases. In recent years, ICIs like pembrolizumab, nivolumab or atezolizumab,  have ushered in a new era in cancer therapy, but their efficacy in HCC is uncertain. In the KEYNOTE-240, patients with previously treated advanced HCC received second-line treatment with pembrolizumab + best supportive care (BSC), or BSC alone. In CheckMate-459 and IMbrave150, patients with advanced HCC received first-line treatment with nivolumab/sorafenib and sorafenib/atezolizumab + bevacizumab, respectively.  

Improved OS, PFS and ORR in patients treated with ICIs

The overall survival (OS) was significantly improved in HCC patients who received ICIs than those on the standard of care (HR [95-%CI]: 0.75[0.62-0.92]; p=0.006). ICIs were also associated with better progression-free survival (PFS) (HR [95%-CI]: 0.74 [0.56-0.97]; p=0.03), and a better overall response rate (ORR) (OR [95%-CI]: 2.82[2.02-3.93]; p<0.001). The probability of adverse events (grade 3-4) was lower in patients who received ICIs than those with sorafenib (OR [95%-CI]: 0.44[0.20-0.96]; p=0.04).

This meta-analysis found superior efficacy and safety associated with ICIs compared with the standard of care . Therefore, these findings suggest that ICIs should become the new standard of care in systemic therapy of unresectable HCC.

Reference

Jácome AA, Castro ACG, Vasconcelos JPS, et al. Efficacy and Safety Associated With Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma: A Meta-analysis. JAMA Netw Open 2021; 4(12):e2136128.

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