Combination of CRAFITY score with Alpha-fetoprotein response predicts a favorable outcome of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

Wei Teng; Chen-Chun Lin; Chung-Wei Su; Po-Ting Lin; Yi-Chung Hsieh; Wei-Ting Chen; Ming-Mo Ho; Ching-Ting Wang; Pei-Mei Chai; Jason Chia-Hsun Hsieh; Chun-Yen Lin; Shi-Ming Lin

Combination of CRAFITY score with Alpha-fetoprotein response predicts a favorable outcome of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

Am J Cancer Res. 2022 Apr 15;12(4):1899-1911. eCollection 2022.

Authors

Wei Teng^{1

2}, Chen-Chun Lin^{1

2}, Chung-Wei Su^{1

2}, Po-Ting Lin^{1

2}, Yi-Chung Hsieh^{1

2}, Wei-Ting Chen^{1

2}, Ming-Mo Ho^{3

2}, Ching-Ting Wang^{4

2}, Pei-Mei Chai^{4

2}, Jason Chia-Hsun Hsieh^{1

5

2}, Chun-Yen Lin^{1

2}, Shi-Ming Lin^{1

2}

Affiliations

¹ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center Taiwan.
² College of Medicine, Chang Gung University Taiwan.
³ Department of Medical Oncology, Chang Gung Memorial Hospital, Linkou Medical Center Taiwan.
⁴ Department of Nursing, Chang Gung Memorial Hospital, Linkou Medical Center Taiwan.
⁵ Division of Hematology-Oncology, Department of Internal Medicine, New Taipei Municipal City Tucheng Hospital Taiwan.

PMID: 35530282
PMCID: PMC9077079

Abstract

Immune checkpoint inhibitors (ICIs) with atezolizumab plus bevacizumab are promising agents for unresectable hepatocellular carcinoma (HCC). We tried to guide the treatment based on recent developed CRAFITY score combining with on-treatment AFP response. Eighty-nine patients who received atezolizumab plus bevacizumab regardless of as a first-line therapy or not for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). The objective response rate (ORR) and disease control rate (DCR) were 25.0% and 65.5%, respectively. Multivariate analysis showed that low CRAFITY score (AFP<100 ng/ml or CRP<10 mg/l) and satisfactory AFP response at 6 weeks (≥75% decrease or ≤10% increase from baseline) were independent factors determining good overall survival (OS) (hazard ratio [HR]=0.143, P=0.002 & HR=0.337, P=0.031), progression-free survival (PFS) (HR=0.419, P=0.022 & HR=0.429, P=0.025) and good responder (odds ratio [OR]=1.763, P=0.044 & OR=3.881, P=0.011). Patients were further divided into three classes by combination of CRAFITY score and AFP response at 6 weeks [The CAR (CRAFITY score and AFP-Response) classification)]: low CRAFITY score with satisfactory AFP response at 6 weeks (class I), either high CRAFITY score or unsatisfactory AFP response at 6 weeks (class II) and high CRAFITY score together with unsatisfactory AFP response at 6 weeks (class III). ORR was 35.0%, 18.2%, and 0% in class I, II and III patients, respectively (overall P=0.034). Patients in the class I had the best OS and PFS, followed by class II and class III (median OS: not reached vs. 11.1 vs. 4.3 months, log-rank P<0.001; median PFS: 7.9 vs. 6.6 vs. 2.6 months, log-rank P=0.001). Combination CRAFITY score and AFP response at 6 weeks with AUROC predicts OS and tumor response to be 0.809 and 0.798, respectively, better than either CRAFITY score (0.771 & 0.750) or AFP response at 6 weeks (0.725 & 0.680) alone. In conclusions, the CAR classification which combining CRAFITY score and AFP response at 6 weeks provides a practical guidance for atezolizumab plus bevacizumab therapy in unresectable HCC patients.

Keywords: CAR classification; atezolizumab plus bevacizumab; hepatocellular carcinoma; prognosis.