Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Andrew X. Zhu; Richard S. Finn; Yoon Koo Kang; Chia Jui Yen; Peter R. Galle; Josep M. Llovet; Eric Assenat; Giovanni Brandi; Kenta Motomura; Izumi Ohno; Bruno Daniele; Arndt Vogel; Tatsuya Yamashita; Chih Hung Hsu; Guido Gerken; John Bilbruck; Yanzhi Hsu; Kun Liang; Ryan C. Widau; Chunxiao Wang; Paolo Abada; Masatoshi Kudo

doi:10.1038/s41416-021-01260-w

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Andrew X. Zhu, Richard S. Finn, Yoon Koo Kang, Chia Jui Yen, Peter R. Galle, Josep M. Llovet, Eric Assenat, Giovanni Brandi, Kenta Motomura, Izumi Ohno, Bruno Daniele, Arndt Vogel, Tatsuya Yamashita, Chih Hung Hsu, Guido Gerken, John Bilbruck, Yanzhi Hsu, Kun Liang, Ryan C. Widau, Chunxiao WangPaolo Abada, Masatoshi Kudo

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Abstract

Background: Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). Methods: Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed. Results: Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001). Conclusions: AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab. Clinical Trial Registration: ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).

Original language	English
Pages (from-to)	1388-1397
Number of pages	10
Journal	British Journal of Cancer
Volume	124
Issue number	8
DOIs	https://doi.org/10.1038/s41416-021-01260-w
State	Published - 12 Apr 2021

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Zhu, A. X., Finn, R. S., Kang, Y. K., Yen, C. J., Galle, P. R., Llovet, J. M., Assenat, E., Brandi, G., Motomura, K., Ohno, I., Daniele, B., Vogel, A., Yamashita, T., Hsu, C. H., Gerken, G., Bilbruck, J., Hsu, Y., Liang, K., Widau, R. C., ... Kudo, M. (2021). Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab. British Journal of Cancer, 124(8), 1388-1397. https://doi.org/10.1038/s41416-021-01260-w

@article{69cdaced9ed3459c8497a3668a9f08ea,

title = "Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab",

abstract = "Background: Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). Methods: Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed. Results: Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001). Conclusions: AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab. Clinical Trial Registration: ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).",

author = "Zhu, {Andrew X.} and Finn, {Richard S.} and Kang, {Yoon Koo} and Yen, {Chia Jui} and Galle, {Peter R.} and Llovet, {Josep M.} and Eric Assenat and Giovanni Brandi and Kenta Motomura and Izumi Ohno and Bruno Daniele and Arndt Vogel and Tatsuya Yamashita and Hsu, {Chih Hung} and Guido Gerken and John Bilbruck and Yanzhi Hsu and Kun Liang and Widau, {Ryan C.} and Chunxiao Wang and Paolo Abada and Masatoshi Kudo",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Cancer Research UK.",

year = "2021",

month = apr,

day = "12",

doi = "10.1038/s41416-021-01260-w",

language = "English",

volume = "124",

pages = "1388--1397",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "8",

}

Zhu, AX, Finn, RS, Kang, YK, Yen, CJ, Galle, PR, Llovet, JM, Assenat, E, Brandi, G, Motomura, K, Ohno, I, Daniele, B, Vogel, A, Yamashita, T, Hsu, CH, Gerken, G, Bilbruck, J, Hsu, Y, Liang, K, Widau, RC, Wang, C, Abada, P & Kudo, M 2021, 'Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab', British Journal of Cancer, vol. 124, no. 8, pp. 1388-1397. https://doi.org/10.1038/s41416-021-01260-w

TY - JOUR

T1 - Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

AU - Zhu, Andrew X.

AU - Finn, Richard S.

AU - Kang, Yoon Koo

AU - Yen, Chia Jui

AU - Galle, Peter R.

AU - Llovet, Josep M.

AU - Assenat, Eric

AU - Brandi, Giovanni

AU - Motomura, Kenta

AU - Ohno, Izumi

AU - Daniele, Bruno

AU - Vogel, Arndt

AU - Yamashita, Tatsuya

AU - Hsu, Chih Hung

AU - Gerken, Guido

AU - Bilbruck, John

AU - Hsu, Yanzhi

AU - Liang, Kun

AU - Widau, Ryan C.

AU - Wang, Chunxiao

AU - Abada, Paolo

AU - Kudo, Masatoshi

PY - 2021/4/12

Y1 - 2021/4/12

N2 - Background: Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). Methods: Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed. Results: Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001). Conclusions: AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab. Clinical Trial Registration: ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).

AB - Background: Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). Methods: Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed. Results: Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001). Conclusions: AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab. Clinical Trial Registration: ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).

UR - http://www.scopus.com/inward/record.url?scp=85100306878&partnerID=8YFLogxK

U2 - 10.1038/s41416-021-01260-w

DO - 10.1038/s41416-021-01260-w

M3 - Article

C2 - 33531690

AN - SCOPUS:85100306878

SN - 0007-0920

VL - 124

SP - 1388

EP - 1397

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 8

ER -

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

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