Efficacy and safety of immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma (HCC): A systematic review and meta-analysis of randomized clinical trials (RCTs).

Authors

null

Alexandre A. Jácome

Grupo Oncoclinicas, Belo Horizonte, Brazil

Alexandre A. Jácome , Ana Carolina Guimaraes De Castro , João Paulo Solar Vasconcelos , Maria Helena Cruz Rangel Silva , Marco Antonio Oliveira Lessa , Eduardo Dias de Moraes , Aline Chaves Andrade , Barbara Sodre Figueiredo Ferreira , Frederico M. T. Lima , Marcela Lima Bulcao , Artur Rodrigues Ferreira , Joao Paulo Fogacci De Farias , Gabriel Prolla , Bernardo Garicochea

Organizations

Grupo Oncoclinicas, Belo Horizonte, Brazil, Oncoclinicas, Belo Horizonte, Brazil, Grupo Oncoclinicas, Salvador, Brazil, Nucleo de Oncologia da Bahia, Salvador, Brazil, Grupo Oncoclinicas, Rio De Janeiro, Brazil, Grupo Oncoclinicas, São Paulo, Brazil, Grupo Oncoclinicas, Porto Alegre, Brazil

Research Funding

No funding received
None

Background: ICIs have ushered a new era in cancer therapy, but their efficacy in HCC is uncertain. Single-arm phase II studies with sorafenib-refractory patients have suggested clinical activity of nivolumab and pembrolizumab, which have become FDA-approved therapies. Nevertheless, the overall effect of ICIs compared with the standard of care (SOC) in unresectable HCC patients is still unknown. Methods: We systematically searched PubMed, Cochrane Library, Web of Science, LILACS, and ASCO and ESMO Meeting Proceedings in the last 10 years for RCTs that have compared the efficacy of ICIs versus the SOC in the systemic therapy of unresectable HCC. Outcomes of interest included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3-4 treatment-related adverse events (TRAEs). A summary hazard ratio (HR) of OS and PFS was calculated using 95% confidence intervals (CI) by fixed-effects model. The likelihood of ICIs being associated with ORR and TRAEs was expressed by odds ratio (OR) and 95% CI using a random-effects model (PROSPERO ID 162599). Results: Of the 2,334 studies yielded by the search, 3 studies were retained (KEYNOTE-240, CheckMate-459, and IMbrave150), totaling 1,657 patients (985 ICIs versus 672 SOC). Two studies compared ICIs versus sorafenib in 1st line setting, and one study compared with placebo in 2nd line. The ICIs studied were pembrolizumab, nivolumab, and atezolizumab. RCTs with anti-CTLA4 have not been reported. Two studies evaluated ICIs as monotherapy, and one study investigated the association with bevacizumab. Compared with the SOC (sorafenib in 1st line or placebo in 2nd line), ICIs significantly improved OS (HR: 0.78, 95% CI 0.68 – 0.89, p = 0.0002), PFS (HR: 0.79, 95% CI 0.71 – 0.89, p < 0.0001), and ORR (OR: 2.82, 95% CI 2.02 – 3.93, p < 0.0001). ICIs were associated with a lower probability of grade 3-4 TRAEs when compared to sorafenib (OR: 0.44, 95% CI 0.20 – 0.96, p = 0.04). No significant heterogeneity was found among studies when OS and ORR were analyzed, but it was found in the analysis of PFS and TRAEs. Conclusions: ICIs demonstrated superior efficacy and safety compared to the standard therapy of patients with unresectable HCC. The analysis of ICIs as monotherapy and combination therapy increased the heterogeneity among studies. The association of anti-angiogenic therapy with ICIs improved the survival benefit of immunotherapy and should become the new SOC in the 1st line systemic therapy of unresectable HCC.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Publication Only

Session Title

Publication Only: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Hepatobiliary Cancer

Citation

J Clin Oncol 38: 2020 (suppl; abstr e16631)

DOI

10.1200/JCO.2020.38.15_suppl.e16631

Abstract #

e16631

Abstract Disclosures

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