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).

• Authors: 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
• Journal: British journal of cancer (Br J Cancer) Vol. 124 Issue 8 Pg. 1388-1397 (04 2021) ISSN: 1532-1827 [Electronic] England
• PMID: 33531690 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• AFP protein, human
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Biomarkers, Tumor
• alpha-Fetoproteins
• ramucirumab

Topics

• Antibodies, Monoclonal, Humanized (administration & dosage, pharmacology)
• Antineoplastic Agents (administration & dosage, pharmacology)
• Biomarkers, Tumor (blood)
• Carcinoma, Hepatocellular (diagnostic imaging, drug therapy, metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Liver Neoplasms (diagnostic imaging, drug therapy, metabolism)
• Prognosis
• Survival Analysis
• Treatment Outcome
• Up-Regulation
• alpha-Fetoproteins (metabolism)