Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: An analysis of the phase 3 REACH study

Ian Chau, Joon Oh Park, Baek Yeol Ryoo, Chia Jui Yen, Ronnie Poon, Davide Pastorelli, Jean Frédéric Blanc, Masatoshi Kudo, Tulio Pfiffer, Etsuro Hatano, Hyun Cheol Chung, Katerina Kopeckova, Jean Marc Phelip, Giovanni Brandi, Shinichi Ohkawa, Chung Pin Li, Takuji Okusaka, Yanzhi Hsu, Paolo B. Abada, Andrew X. Zhu

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Background: Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH. Methods: Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed. Results: Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001). Conclusions: Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.

Original languageEnglish
Pages (from-to)19-26
Number of pages8
JournalBritish journal of cancer
Issue number1
Publication statusPublished - 2018 Jul 3

Bibliographical note

Funding Information:
Competing interests: I.C. reports advisory board roles at Sanofi Oncology, Eli Lilly and Company, Bristol Meyers Squibb, MSD, Bayer, Roche, Five Prime Therapeutics; honoraria from Taiho, Pfizer, Amgen, Eli-Lilly, Gilead Science; research funding from Janssen-Cilag, Sanofi Oncology, Merck-Serono, Novartis. J.O.P. reports receiving clinical research grants, honoraria from Celgene and research grant from AstraZeneca. He reports a role on the advisory board for Celgene. J.-F.B. reports payments from Lilly Oncology, Bayer SP, BMS and Novartis outside the submitted work. M.K. received research grants from Chugai, Otsuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Eisai, Bayer, Abbvie, Medico’s Hirata, Astellas Pharma and Bristol-Myers Squibb; lecture fees from Bayer, Eisai, MSD, Ajinomoto, Kowa and Taiho; and consulting fees from Kowa, MSD, BMS, Bayer, Chugai, Taiho and Eisai. H.C. C. is a consultant for Eli Lilly and Company, MSD, Merck-Serono, Taiho, BMS, Celltrion, he has received research grants from Eli Lilly and Company, GSK and MSD. J.-M.P. reports receiving research grants from Roche and Merck and payments from Eli Lilly and Company, Bayer, Sanofi, Roche and Merck. T.O. reports research grants, advisory role and honoraria from Eli Lilly, during the conduct of the study; he also reports research grants advisory role and/or honoraria from Novartis Pharma K.K., Kowa K.K., Takeda Bio Development Center Limited, Nippon Boehringer Ingelheim Co., Ltd., Dainippon Simitomo Pharma Co., Ltd., Pfizer Jana Inc, Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Yakuruto Honsha Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd, AstraZeneca K.K., Merck Serono Co., Ltd., OncoTherapy Science Inc., Kyowa Hakko Kirin Co., Ltd., Shizuoka Industry, Baxter, Nano Carrier Co., Ltd., Zeria Pharmaceutical Co., Ltd., Glaxo Smith Kline K.K., Nobelpharma Co., Ltd., burisutoru, Nipponchemofa, EA Pharma Co., Ltd., FUJIFILM RI Pharma Co., Ltd., Astellas Pharma Inc., Nippon Kayaku Co., Ltd., Daiichi Sankyo Co., Ltd., J-CRSU CO., LTD., outside the submitted work. P.A. and Y.H. are employees of Eli Lilly and Company and own stock from Eli Lilly and Company. A.X.Z. reports that his institution received research support from Eli Lilly and Company. The other authors declare no competing interests.

Funding Information:
This study was funded by Eli Lilly and Company. We thank the patients, their families and the study personnel across all sites for participating in this study. Yihuan Xu of Eli Lilly and Company (Bridgewater, NJ) provided statistical expertise. Nathalie Godinot of Eli Lilly and Company (Indianapolis, IN) provided writing assistance. I.C. would like to thank the National Health Service for funding to the National Institute for Health Research Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.

Publisher Copyright:
© 2018 The Author(s).

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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