Early alpha-foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma.
Adult
Aged
Angiogenesis Inhibitors
/ therapeutic use
Antineoplastic Agents, Immunological
/ urine
Biomarkers, Tumor
/ blood
Carcinoma, Hepatocellular
/ drug therapy
Female
Humans
Liver Neoplasms
/ drug therapy
Male
Middle Aged
Survival Analysis
Taiwan
Treatment Outcome
alpha-Fetoproteins
/ metabolism
advanced hepatocellular carcinoma
alpha-fetoprotein
alpha-foetoprotein
biomarker
immune checkpoint inhibitors
immunotherapy
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
03
07
2019
revised:
25
07
2019
accepted:
30
07
2019
pubmed:
11
8
2019
medline:
21
10
2020
entrez:
11
8
2019
Statut:
ppublish
Résumé
Post-treatment decline in serum alpha-foetoprotein (AFP) levels has been shown to predict the treatment efficacy of antiangiogenic therapy for advanced hepatocellular carcinoma (HCC). We explored whether a decline in AFP levels was also associated with treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with advanced HCC. We reviewed all patients who received ICI therapy for advanced HCC. AFP response was evaluated in patients with the pretreatment AFP level of >20 ng/mL. We defined early AFP response as a >20% decline in serum AFP levels within the first 4 weeks of treatment initiation relative to pretreatment levels. We then studied whether early AFP response was associated with treatment outcomes. Sixty patients were enrolled in this study; 43 of them were evaluable for early AFP response. The objective response rate of early AFP responders was significantly higher than that of early AFP nonresponders (73% vs. 14%, P < .001). Early AFP responders, compared with early AFP nonresponders, exhibited significantly longer overall survival (OS) (median, 28.0 vs 11.2 months, P = .048) and progression-free survival (PFS) (median, 15.2 vs 2.7 months, P = .002). After adjusting for other clinicopathological variables and treatments, early AFP response remained an independent predictor for longer OS (hazard ratio [HR] = 0.089, 95% confidence interval [CI] = 0.018-0.441; P = .003) and PFS (HR = 0.128, 95% CI = 0.041-0.399; P < .001). Early AFP response was associated with higher treatment efficacy of ICIs for advanced HCC. Additional validation studies are nonetheless warranted.
Sections du résumé
BACKGROUND
Post-treatment decline in serum alpha-foetoprotein (AFP) levels has been shown to predict the treatment efficacy of antiangiogenic therapy for advanced hepatocellular carcinoma (HCC). We explored whether a decline in AFP levels was also associated with treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with advanced HCC.
METHODS
We reviewed all patients who received ICI therapy for advanced HCC. AFP response was evaluated in patients with the pretreatment AFP level of >20 ng/mL. We defined early AFP response as a >20% decline in serum AFP levels within the first 4 weeks of treatment initiation relative to pretreatment levels. We then studied whether early AFP response was associated with treatment outcomes.
RESULTS
Sixty patients were enrolled in this study; 43 of them were evaluable for early AFP response. The objective response rate of early AFP responders was significantly higher than that of early AFP nonresponders (73% vs. 14%, P < .001). Early AFP responders, compared with early AFP nonresponders, exhibited significantly longer overall survival (OS) (median, 28.0 vs 11.2 months, P = .048) and progression-free survival (PFS) (median, 15.2 vs 2.7 months, P = .002). After adjusting for other clinicopathological variables and treatments, early AFP response remained an independent predictor for longer OS (hazard ratio [HR] = 0.089, 95% confidence interval [CI] = 0.018-0.441; P = .003) and PFS (HR = 0.128, 95% CI = 0.041-0.399; P < .001).
CONCLUSION
Early AFP response was associated with higher treatment efficacy of ICIs for advanced HCC. Additional validation studies are nonetheless warranted.
Substances chimiques
Angiogenesis Inhibitors
0
Antineoplastic Agents, Immunological
0
Biomarkers, Tumor
0
alpha-Fetoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2184-2189Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-390.
Cheng A-L, Kang Y-K, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25-34.
El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389:2492-2502.
Zhu AX, Finn RS, Edeline J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018;19:940-952.
Finn RS, Ryoo BY, Merle P, et al. Results of KEYNOTE- 240: phase 3 study of pembrolizumab vs best supportive care for second line therapy in advanced hepatocellular carcinoma. J Clin Oncol. 2019;37(15_suppl): 4004-4004.
Squibb B-M. Bristol-Myers Squibb Announces Results from CheckMate -459 Study Evaluating Opdivo (nivolumab) as a First-Line Treatment for Patients with Unresectable Hepatocellular Carcinoma. https://news.bms.com/press-release/bmy/bristol-myers-squibb-announces-results-checkmate-459-study-evaluating-opdivo-nivol. Accessed July 19, 2019.
Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509-2520.
Bonneville R, Krook MA, Kautto EA, et al. Landscape of microsatellite instability across 39 cancer types. JCO Precis Oncol. 2017; 1-15. https://doi.org/10.1200/PO.17.00073
Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208-1236.
Chan SL, Mo FK, Johnson PJ, et al. New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J Clin Oncol. 2009;27:446-452.
Chen L-T, Liu T-W, Chao Y, et al. Alpha-fetoprotein response predicts survival benefits of thalidomide in advanced hepatocellular carcinoma. Aliment Pharmacol Ther. 2005;22:217-226.
Vora SR, Zheng H, Stadler ZK, Fuchs CS, Zhu AX. Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist. 2009;14:717-725.
Shao Y-Y, Chen B-B, Ou D-L, et al. Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy. Aliment Pharmacol Ther. 2017;46:722-730.
Shao YY, Lin ZZ, Hsu C, Shen YC, Hsu CH, Cheng AL. Early alpha-fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma. Cancer. 2010;116:4590-4596.
Sanchez A, Roces LV, Garcia IZ, et al. Value of alpha-fetoprotein as an early biomarker for treatment response to sorafenib therapy in advanced hepatocellular carcinoma. Oncol Lett. 2018;15:8863-8870.
Lee S, Kim BK, Kim SU, et al. Early alpha-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib. J Hepatocell Carcinoma. 2015;2:39-47.
Minata M, Nishida N, Komeda T, et al. Postoperative detection of alpha-fetoprotein mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma. J Gastroenterol Hepatol. 2001;16:445-451.
Ijichi M, Takayama T, Matsumura M, Shiratori Y, Omata M, Makuuchi M. Alpha-Fetoprotein mRNA in the circulation as a predictor of postsurgical recurrence of hepatocellular carcinoma: a prospective study. Hepatology. 2002;35:853-860.
Peng SY, Chen WJ, Lai PL, Jeng YM, Sheu JC, Hsu HC. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer. 2004;112:44-50.
Poon RT, Ho JW, Tong CS, Lau C, Ng IO, Fan ST. Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma. Br J Surg. 2004;91:1354-1360.
Snowberger N, Chinnakotla S, Lepe RM, et al. Alpha fetoprotein, ultrasound, computerized tomography and magnetic resonance imaging for detection of hepatocellular carcinoma in patients with advanced cirrhosis. Aliment Pharmacol Ther. 2007;26:1187-1194.
Furihata T, Sawada T, Kita J, et al. Serum alpha-fetoprotein level per tumor volume reflects prognosis in patients with hepatocellular carcinoma after curative hepatectomy. Hepatogastroenterology. 2008;55:1705-1709.
Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20:282-296.
Meyer T, Melero I, Yau T, et al. Safety and biomarker assessments in sorafenib-experienced patients with advanced hepatocellular carcinoma treated with nivolumab in the checkmate-040 study. J Hepatol. 2018;68(suppl 1):S16.