Using Modified RECIST and Alpha-Fetoprotein Levels to Assess Treatment Benefit in Hepatocellular Carcinoma.
OBJECTIVE
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.
Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France.
Jean-Luc
JL
Raoul
National Cancer Center, Goyang, Republic of Korea.
Joong-Won
JW
Park
Asan Medical Center, Seoul, Republic of Korea.
Yoon-Koo
YK
Kang
Geffen School of Medicine, UCLA, Los Angeles, Calif., USA.
Richard S
RS
Finn
Korea University Guro Hospital, Seoul, Republic of Korea.
Jun Suk
JS
Kim
The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
Winnie
W
Yeo
The University of Chicago Medical Center, Chicago, Ill., USA.
Blasé N
BN
Polite
Veterans General Hospital, Taiwan, Republic of China.
Yee
Y
Chao
Bristol-Myers Squibb, Princeton, N.J., USA.
Ian
I
Walters
Bristol-Myers Squibb, Braine l'Alleud, Belgium.
Christine
C
Baudelet
Pisa University Hospital, Pisa, Italy.
Riccardo
R
Lencioni
Alpha-fetoprotein; Brivanib; Hepatocellular carcinoma; WHO criteria; mRECIST