Early alpha‐foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma

Shao, Yu‐Yun; Liu, Tsung-Hao; Hsu, Chiun; Lu, Li-Chun; Shen, Yin-Chung; Lin, Zhong‐Zhe; Cheng, Ann‐Lii; Hsu, Chih‐Hung

doi:10.1111/liv.14210

Cited by 62 publications

(58 citation statements)

References 23 publications

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“…Among 43 patients who received immune checkpoint inhibitor therapy in clinical trials for advanced HCC at a medical referral centre in Taiwan, early AFP response (defined as >20% decline in serum AFP levels within the first 4 weeks of treatment initiation) was associated with higher treatment efficacy. 39 AFP responders exhibited significantly longer OS (median, 28.0 vs. 11.2 months) and PFS (median, 15.2 vs. 2.7 months) compared with AFP nonresponders. These differences in survival outcomes remained after adjusting for multiple variables, including various treatments.…”

Section: Discussionmentioning

confidence: 93%

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

et al. 2021

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Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed. Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001). Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab. Clinical Trial Registration ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).

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Section: Discussionmentioning

confidence: 93%

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

et al. 2021

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“…In a recent real-life experience of ICI-treated HCC, no factor was identified to associate with response, either [19]. Early AFP reduction >20% within the first 4 weeks of ICI treatment was recently reported in relation to treatment efficacy for patients with baseline AFP > 20 ng/mL [20]. In this study, we proposed a novel 10-10 rule to early predict ICI response based on baseline AFP level ≥10 ng/mL, and 10% reduction within 4 weeks of treatment.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Response and Survival in Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma

Lee

Chao

Chen

et al. 2020

Cancers

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Immune checkpoint inhibitors (ICIs) with nivolumab and pembrolizumab are promising agents for advanced hepatocellular carcinoma (HCC) but lack of effective biomarkers. We aimed to investigate the potential predictors of response and factors associated with overall survival (OS) for ICI treatment in unresectable HCC patients. Ninety-five patients who received nivolumab or pembrolizumab for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on RECIST v1.1. Factors associated with outcomes were analyzed. Of 90 patients with evaluable images, the objective response rate (ORR) was 24.4%. Patients at Child–Pugh A or received combination treatment had higher ORR. Early alpha-fetoprotein (AFP) >10% reduction (within 4 weeks) was the only independent predictor of best objective response (odds ratio: 7.259, p = 0.001). For patients with baseline AFP ≥10 ng/mL, significantly higher ORR (63.6% vs. 10.2%, p < 0.001) and disease control rate (81.8% vs. 14.3%, p < 0.001) were observed in those with early AFP reduction than those without. In addition, early AFP reduction and albumin-bilirubin (ALBI) grade or Child–Pugh class were independent factors associated with OS in different models. In conclusion, a 10-10 rule of early AFP response can predict objective response and survival to ICI treatment in unresectable HCC. ALBI grade and Child–Pugh class determines survival by ICI treatment.

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“…Such an early AFP response (>20% reduction in AFP levels after first 4 weeks of ICB therapy) could accurately predict the efficacy of ICB therapy. For instance, early AFP responders who had pre-treatment AFP level of >20 ng/mL showed significantly longer overall survival and progression-free survival as compared to non-responders (102). In this study, ∼50% of AFP non-responders exhibited progressive disease during the first assessment and none of them achieved a complete or partial response later.…”

Section: Serum Tumor Markersmentioning

confidence: 49%

“…Immune cell counts, lymphocytes phenotype and serum protein signature such as IL-8 have been suggested to be associated with clinical outcome of cancer patients who were primarily treated with ICB (96)(97)(98)(99)(100). In addition, the serum tumor markers and circulating tumor DNA were also observed to be associated with response (101)(102)(103).…”

Section: Circulating Prognostic Biomarkersmentioning

confidence: 99%

Progress and Challenges of Predictive Biomarkers for Immune Checkpoint Blockade

Lei

Huang

et al. 2021

Front. Oncol.

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Over the past decade, immune checkpoint blockade (ICB) therapy has revolutionized the outlook for oncology with significant and sustained improvement in the overall patient survival. Unlike traditional cancer therapies, which target the cancer cells directly, ICB acts on the immune system to enhance anti-tumoral immunity. However, the response rate is still far from satisfactory and most patients are refractory to such treatment. Unfortunately, the mechanisms underlying such heterogeneous responses between patients to ICB therapy remain unclear. In addition, escalating costs of cancer care and unnecessary immune-related adverse events also are pertinent considerations with applications of ICB. Given these issues, identifying explicit predictive biomarkers for patient selection is an urgent unmet need to increase the efficacy of ICB therapy. The markers can be classified as tumor related and non-tumor-related biomarkers. Although substantial efforts have been put into investigating various biomarkers, none of them has been found to be sufficient for effectively stratifying patients who may benefit from immunotherapy. The present write up is an attempt to review the various emerging clinically relevant biomarkers affecting the efficacy of immune checkpoint inhibitors, as well as the limitations associated with their clinical application.

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Early alpha‐foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma

Cited by 62 publications

References 23 publications

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Predictors of Response and Survival in Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma

Progress and Challenges of Predictive Biomarkers for Immune Checkpoint Blockade

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