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

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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:, REACH (NCT01140347) and REACH-2 (NCT02435433).

Original languageEnglish
Pages (from-to)1388-1397
Number of pages10
JournalBritish Journal of Cancer
Issue number8
StatePublished - 12 Apr 2021


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