Immune Checkpoint Inhibitors Likely Best Standard Therapies for Unresectable Liver Cancer

By Marilynn Larkin

December 20, 2021

NEW YORK (Reuters Health) - In patients with unresectable hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICIs) were associated with superior efficacy and safety compared with standard therapies in a meta-analysis.

Dr. Alexandre Jácome of Oncoclínicas of Belo Horizonte in Brazil said he was surprised by the findings "because ICIs showed superior efficacy and safety compared to the standard of care in all endpoints: overall survival, progression-free survival, overall response rate and treatment-related adverse events."

"Guidelines consider ICIs in combination with anti-angiogenics as first-line therapy for unresectable HCC, but they still recommend tyrosine kinase inhibitors for patients not eligible for anti-angiogenic therapy," he noted.

"Based on the results of our study," he said, "ICIs should be the therapy of choice for first-line therapy, either in combination or as monotherapy, and the standard of care in second-line therapy for those patients who have not previously received them."

As reported in JAMA Network Open, Dr. Jácome and colleagues searched the literature from 2010-2020 for randomized clinical trials comparing ICIs versus standard therapies for unresectable HCC.

The primary outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and treatment-related adverse events (TRAEs).

Three (of 1,836) studies were included, with a total of 1,657 patients (985 treated with ICIs vs. 672 receiving standard treatment).

Two studies evaluated ICIs as monotherapy, and one looked at the combination of ICIs with bevacizumab.

Compared with standard therapies - i.e., sorafenib in first-line therapy or placebo in second-line therapy - ICIs were associated with significantly improved OS (HR, 0.75), PFS (HR, 0.74), and ORR (OR, 2.82), as Dr. Jácome indicated.

The probability of grade 3 or 4 TRAEs was lower with ICIs than with sorafenib (OR, 0.44).

The authors conclude, "This meta-analysis...highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC."

Dr. Danielle DePeralta, a hepatopancreatobiliary surgeon at Northwell Health Cancer Institute in Lake Success, New York, commented in an email to Reuters Health, "Systemic therapy options (for unresectable HCC) were previously limited to sorafenib, but over the last four years several new agents including atezolizumab (an anti-PDL1 inhibitor), plus bevacizumab have been approved for first- or second-line therapy. While this is exciting, it can be difficult to know how to best incorporate and sequence these agents."

"The authors report improved outcomes and less toxicity with ICIs, which was primarily driven by the IMbrave150 study," she said. "I agree with the authors that based on this study, in appropriately selected patients, dual therapy with atezolizumab plus bevacizumab has replaced sorafenib as the preferred first-line treatment."

"However," she added, "many patients are not candidates for dual therapy because of bleeding risk, autoimmune disease, or coinfection with hepatitis B and C."

"Moving forward, we desperately need better ways to personalize our treatment approach and predict in advance which patients are most likely to respond to ICIs and which patients will do better with other therapies," she said.

"We have seen amazing responses with ICIs, but only in a minority of patients," she noted. "As a surgeon, I am particularly interested in how we can leverage these agents to downstage patients with unresectable HCC such that they become candidates for surgical resection and potential cure."

SOURCE: https://bit.ly/3q3dGMU JAMA Network Open, online December 6, 2021.

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