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Review
. 2014 Oct;3(3-4):439-50.
doi: 10.1159/000343872.

Using Modified RECIST and Alpha-Fetoprotein Levels to Assess Treatment Benefit in Hepatocellular Carcinoma

Jean-Luc Raoul  1 , Joong-Won Park  2 , Yoon-Koo Kang  3 , Richard S Finn  4 , Jun Suk Kim  5 , Winnie Yeo  6 , Blasé N Polite  7 , Yee Chao  8 , Ian Walters  9 , Christine Baudelet  10 , Riccardo Lencioni  11
Affiliations
Review

Using Modified RECIST and Alpha-Fetoprotein Levels to Assess Treatment Benefit in Hepatocellular Carcinoma

Jean-Luc Raoul et al. Liver Cancer. 2014 Oct.

Abstract

Background and aims: Assessing treatment responses in hepatocellular carcinoma (HCC) is challenging, and alternative radiologic methods of measuring treatment response are required. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC and alpha-fetoprotein (AFP) levels were assessed in a post hoc analysis of a phase II study of brivanib, a selective dual inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling.

Methods: HCC patients were treated with first-line (cohort A; n = 55) or second-line (cohort B; n = 46) brivanib alaninate 800 mg once daily. Outcomes were compared between World Health Organization (WHO) criteria and (retrospectively by) mRECIST by independent review. The relationship between on-study AFP changes and outcome was analyzed in patients with elevated AFP at baseline.

Results: Response rates were higher with mRECIST versus WHO criteria in cohorts A (25.5% vs. 7.3%) and B (10.9% vs. 4.3%). Progressive disease (PD) as assessed by mRECIST was associated with a very short median overall survival (OS; cohort A, 2.8 months; cohort B, 5.3 months); PD as assessed by WHO criteria reflected a mixed population of patients with better outcomes. mRECIST responders tended to have a>50% AFP decrease during therapy. In cohorts A and B pooled, an early AFP response (>20%or >50% decline from baseline within the first 4 weeks) was not associated with longer median OS.

Conclusions: Tumor response as assessed by mRECIST differed from that by WHO criteria, with mRECIST possibly identifying true nonresponders with a poor prognosis. Many patients had AFP decreases correlating with tumor shrinkage, yet an association with long-term benefit was unclear. mRECIST and on-treatment AFP levels are being explored further with brivanib in HCC.

Keywords: Alpha-fetoprotein; Brivanib; Hepatocellular carcinoma; WHO criteria; mRECIST.

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Figures

Fig. 1
Fig. 1
Example of a patient treated with first-line brivanib alaninate 800 mg once daily (cohort A) who was initially assessed as having PR by WHO criteria. On scan reassessment by mRECIST, this patient was classified as having CR. Adapted with permission from Park JW, Finn RS, Kim JS, et al. Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma. As described by Park JW, et al. [15].
Fig. 2
Fig. 2
Overall survival (a) and 3-month landmark overall survival (b) of cohort A according to disease control status.
Fig. 3
Fig. 3
Overall survival (a) and 3-month landmark overall survival (b) of cohort B according to disease control status.
Fig. 4
Fig. 4
Best decrease from baseline in AFP level according to mRECIST in treatment-naïve patients (a) and in patients who had received prior therapy (b) Only patients with baseline AFP levels greater than the upper limit of normal (approximately 10 ng/ml [range: 8-24 ng/ml]) and at least one on-study AFP assessment were included.
See this image and copyright information in PMC

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