Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score.
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Scheiner Bernhard, Pomej Katharina, Kirstein Martha M, Hucke Florian, Finkelmeier Fabian, Waidmann Oliver, Himmelsbach Vera, Schulze Kornelius, von Felden Johann, Fründt Thorben W, Stadler Marc, Heinzl Harald, Shmanko Kateryna, Spahn Stephan, Radu Pompilia, Siebenhüner Alexander R, Mertens Joachim C, Rahbari Nuh N, Kütting Fabian, Waldschmidt Dirk-Thomas, Ebert Matthias P, Teufel Andreas, De Dosso Sara, Pinato David J, Pressiani Tiziana, Meischl Tobias, Balcar Lorenz, Müller Christian, Mandorfer Mattias, Reiberger Thomas, Trauner Michael, Personeni Nicola, Rimassa Lorenza, Bitzer Michael, Trojan Jörg, Weinmann Arndt, Wege Henning, Dufour Jean-François, Peck-Radosavljevic Markus, Vogel Arndt, Pinter Matthias
Аннотация
METHODS: Patients with HCC put on PD-(L)1-based immunotherapy were included in a training set (n = 190; 6 European centers) and a validation set (n = 102; 8 European centers). We investigated the prognostic value of baseline variables on overall survival using a Cox model in the training set and developed the easily applicable CRAFITY (CRP and AFP in ImmunoTherapY) score. The score was validated in the independent, external cohort, and evaluated in a cohort of patients treated with sorafenib (n = 204).
RESULTS: Baseline serum alpha-fetoprotein ≥100 ng/ml (hazard ratio [HR] 1.7; p = 0.007) and C-reactive protein ≥1 mg/dl (HR, 1.7; p = 0.007) were identified as independent prognostic factors in multivariable analysis and were used to develop the CRAFITY score. Patients who fulfilled no criterion (0 points; CRAFITY-low) had the longest median overall survival (27.6 (95% CI 19.5-35.8) months), followed by those fulfilling 1 criterion (1 point; CRAFITY-intermediate; 11.3 (95% CI 8.0-14.6) months), and patients meeting both criteria (2 points; CRAFITY-high; 6.4 (95% CI 4.8-8.1) months; p <0.001). Additionally, best radiological response (complete response/partial response/stable disease/progressive disease) was significantly better in patients with lower CRAFITY score (CRAFITY-low: 9%/20%/52%/20% vs. CRAFITY-intermediate: 3%/25%/36%/36% vs. CRAFITY-high: 2%/15%/22%/61%; p = 0.003). These results were confirmed in the independent validation set and in different subgroups, including Child-Pugh A and B, performance status 0 and ≥1, and first-line and later lines. In the sorafenib cohort, CRAFITY was associated with survival, but not radiological response.
CONCLUSIONS: The CRAFITY score is associated with survival and radiological response in patients receiving PD-(L)1 immunotherapy. The score may help with patient counseling but requires prospective validation.
LAY SUMMARY: The immunotherapy-based regimen of atezolizumab plus bevacizumab represents the new standard of care in systemic first-line therapy of hepatocellular carcinoma (HCC). Biomarkers to predict treatment outcome are an unmet need in patients undergoing immunotherapy for HCC. We developed and externally validated a score that predicts outcome in patients with HCC undergoing immunotherapy with immune checkpoint blockers.