Using modified RECIST and alpha-fetoprotein levels to assess treatment benefit in hepatocellular carcinoma

Jean Luc Raoul, Joong Won Park, Yoon Koo Kang, Richard S. Finn, Jun Suk Kim, Winnie Yeo, Blasé N. Polite, Yee Chao, Ian Walters, Christine Baudelet, Riccardo Lencioni

Research output: Contribution to journalReview article

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)439-450
Number of pages12
JournalLiver Cancer
Volume3
Issue number3-4
DOIs
StatePublished - Apr 16 2014
Externally publishedYes

Fingerprint

alpha-Fetoproteins
Hepatocellular Carcinoma
Therapeutics
Fibroblast Growth Factors
Response Evaluation Criteria in Solid Tumors
Vascular Endothelial Growth Factor A
Neoplasms
Survival
Population

Keywords

  • Alpha-fetoprotein
  • Brivanib
  • Hepatocellular carcinoma
  • mRECIST
  • WHO criteria

ASJC Scopus subject areas

  • Hepatology
  • Oncology

Cite this

Raoul, J. L., Park, J. W., Kang, Y. K., Finn, R. S., Kim, J. S., Yeo, W., ... Lencioni, R. (2014). Using modified RECIST and alpha-fetoprotein levels to assess treatment benefit in hepatocellular carcinoma. Liver Cancer, 3(3-4), 439-450. https://doi.org/10.1159/000343872

Using modified RECIST and alpha-fetoprotein levels to assess treatment benefit in hepatocellular carcinoma. / Raoul, Jean Luc; Park, Joong Won; Kang, Yoon Koo; Finn, Richard S.; Kim, Jun Suk; Yeo, Winnie; Polite, Blasé N.; Chao, Yee; Walters, Ian; Baudelet, Christine; Lencioni, Riccardo.

In: Liver Cancer, Vol. 3, No. 3-4, 16.04.2014, p. 439-450.

Research output: Contribution to journalReview article

Raoul, JL, Park, JW, Kang, YK, Finn, RS, Kim, JS, Yeo, W, Polite, BN, Chao, Y, Walters, I, Baudelet, C & Lencioni, R 2014, 'Using modified RECIST and alpha-fetoprotein levels to assess treatment benefit in hepatocellular carcinoma', Liver Cancer, vol. 3, no. 3-4, pp. 439-450. https://doi.org/10.1159/000343872
Raoul, Jean Luc ; Park, Joong Won ; Kang, Yoon Koo ; Finn, Richard S. ; Kim, Jun Suk ; Yeo, Winnie ; Polite, Blasé N. ; Chao, Yee ; Walters, Ian ; Baudelet, Christine ; Lencioni, Riccardo. / Using modified RECIST and alpha-fetoprotein levels to assess treatment benefit in hepatocellular carcinoma. In: Liver Cancer. 2014 ; Vol. 3, No. 3-4. pp. 439-450.
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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.",
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AU - Raoul, Jean Luc

AU - Park, Joong Won

AU - Kang, Yoon Koo

AU - Finn, Richard S.

AU - Kim, Jun Suk

AU - Yeo, Winnie

AU - Polite, Blasé N.

AU - Chao, Yee

AU - Walters, Ian

AU - Baudelet, Christine

AU - Lencioni, Riccardo

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N2 - 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.

AB - 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.

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KW - Brivanib

KW - Hepatocellular carcinoma

KW - mRECIST

KW - WHO criteria

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