Abstract
Simple SummaryThe investigation of predictive and prognostic markers is pivotal in patients affected by hepatocellular carcinoma treated with immune-checkpoint-inhibitors. Inflammation has a central role in hepatocellular carcinoma development and progression; however, its role in influencing outcomes in the context of immunotherapy has not been fully elucidated yet. In the following study, we investigated the prognostic role of bloods derived inflammatory markers and we found that they predict survival and response of patients treated with immunotherapy for advanced hepatocellular carcinoma.Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic responses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45–2.64, p < 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.
Highlights
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide [1] with only 24% of patients being disease-free at 5 years, even after curative resection [2]
Nivolumab failed to significantly improve survival compared to sorafenib in the first-line CheckMate 459 study [5] and pembrolizumab was not demonstrated to perform better than placebo in the second-line Keynote-240 clinical trial [6], but it has recently been reported to significantly improve overall survival (OS), progression free survival (PFS), and objective response rate (ORR) compared to placebo in Asian patients treated after sorafenib failure within the phase III Keynote-394 trial (NCT03062358)
We evaluated the prognostic value of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) in HCC patients treated with immune checkpoint inhibitors (ICIs)
Summary
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide [1] with only 24% of patients being disease-free at 5 years, even after curative resection [2]. The forerunners PD-1 blocking antibodies nivolumab and pembrolizumab have demonstrated a response in a little less than 20% of patients with HCC [4], and have yielded controversial results in phase III clinical trials. Available measures of systemic inflammation, such as the neutrophil-lymphocyte ratio (NLR) [18], platelet-lymphocyte ratio (PLR) and prognostic nutritional index (PNI) [19], have been previously validated for their survival outcome in HCC prior to clinical use of ICIs [13,20]. These markers have the advantage of being non-invasive, inexpensive, and easy to obtain in routine practice. We evaluated the prognostic value of NLR, PLR, and PNI in HCC patients treated with ICIs
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