Immune checkpoint inhibitors (ICIs) may be more effective than standard care for patients with unresectable hepatocellular carcinoma (HCC), according to a meta-analysis published in JAMA Network Open.

The meta-analysis included 3 randomized, phase 3 trials — KEYNOTE-240, CheckMate-459, and IMbrave150. In KEYNOTE-240 (ClinicalTrials.gov Identifier: NCT02702401), patients with previously treated, advanced HCC received pembrolizumab plus best supportive care (BSC) or BSC alone.

In CheckMate-459 (ClinicalTrials.gov Identifier: NCT02576509), patients with advanced HCC received first-line treatment with nivolumab or sorafenib. In IMbrave150 (ClinicalTrials.gov Identifier: NCT03434379), patients with advanced HCC received first-line sorafenib or atezolizumab plus bevacizumab. 

The trials included a total of 1657 patients — 985 treated with ICIs and 672 receiving standard treatment.


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Overall, patients who received ICIs had better overall survival (OS) compared with patients who received standard care. The hazard ratio (HR) was 0.75 (95% CI, 0.62-0.92; P =.006).

When looking at the 3 trials individually, OS was only significantly better with ICIs in the IMbrave150 trial (P <.001). The between-arm differences did not reach the predefined threshold for significance in KEYNOTE-240 (P =.02) or CheckMate-459 (P =.07).

Overall, patients who received ICIs had better progression-free survival (PFS) than those who received standard care, with an HR of 0.74 (95% CI, 0.56-0.97; P =.03). PFS was significantly better with ICIs in both KEYNOTE-240 (P =.0022) and IMbrave150 (P <.001) but not in CheckMate-459.  

Overall, ICIs were associated with better overall response rates (ORRs), with an odds ratio (OR) of 2.82 (95% CI, 2.02-3.93; P <.001). ORRs were higher with ICIs in each of the trials individually as well.

Lastly, ICIs were associated with a lower probability of grade 3-4 treatment-related adverse events when compared with sorafenib (OR, 0.44; 95% CI, 0.20-0.96; P =.04).

“These findings suggest that ICIs should be the new standard of care in systemic therapy of unresectable HCC,” the researchers wrote.

Because the overall benefit observed with ICIs was largely due to data from the IMbrave150 trial, the researchers concluded that atezolizumab plus bevacizumab “should be preferentially used in the first-line setting in eligible patients.”

They noted, however, that the best choice of treatment after unsuccessful dual therapy is not yet clear.

Disclosures: KEYNOTE-240 was sponsored by Merck Sharp & Dohme Corp, IMbrave150 was sponsored by Hoffmann-La Roche, and CheckMate-459 was sponsored by Bristol-Myers Squibb in collaboration with Ono Pharmaceutical Co. Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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. doi:10.1001/jamanetworkopen.2021.36128