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Thématique :
- Carcinome hépatocellulaire (CHC)
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Originalité :
Très original
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Pas encore
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Nom du veilleur :
Docteur Jean-Louis PAYEN
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Journal of Hepatology
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2016/08
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2016 Aug;65(2):289-95
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doi: 10.1016/j.jhep.2016.04.004
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Randomized phase II placebo controlled study of codrituzumab in previously treated patients with advanced hepatocellular carcinoma
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Abou-Alfa GK, Puig O, Daniele B, Kudo M, Merle P, Park JW, Ross P, Peron JM, Ebert O, Chan S, Poon TP, Colombo M, Okusaka T, Ryoo BY, Minguez B, Tanaka T, Ohtomo T, Ukrainskyj S, Boisserie F, Rutman O, Chen YC, Xu C, Shochat E, Jukofsky L, Reis B, Chen G, Di Laurenzio L, Lee R, Yen CJ
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https://www.ncbi.nlm.nih.gov/pubmed/?term=Randomized+phase+II+placebo+controlled+study+of+codrituzumab+in+previously+treated+patients+with+advanced+hepatocellular+carcinoma
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BACKGROUND & AIMS:
Codrituzumab, a humanized monoclonal antibody against Glypican-3 (GPC3) that is expressed in hepatocellular carcinoma (HCC), interacts with CD16/FcγRIIIa and triggers antibody-dependent cytotoxicity. Codrituzumab was studied vs. placebo in a randomized phase II trial in advanced HCC patients who had failed prior systemic therapy.
METHODS:
Patients with advanced HCC who had failed prior systemic therapy, ⩾18years, Eastern cooperative oncology group (ECOG) 0-1, Child-Pugh A were randomized 2:1 to biweekly codrituzumab 1600mg vs. placebo. Patients were stratified based on GPC3 immunohistochemical expression: 2+/3+, 1+, and 0. Primary endpoint was progression free survival. Secondary endpoints include overall survival (OS), tolerability, pharmacokinetics, and an exploratory endpoint in biomarkers analysis.
RESULTS:
185 patients were enrolled: 125 received codrituzumab and 60 placebo: Median age 64/63, 85/75% male, 46/42% Asian, ECOG 0 65/63%, 74/77% having vascular invasion and/or extra-hepatic metastasis. 84%/70% had prior sorafenib. Drug exposure was 98.4% of planned dose, with an identical adverse events profile between the 2 groups. The median progression free survival and overall survival in the codrituzumab vs. placebo groups in months were: 2.6 vs. 1.5 (hazard ratios 0.97, p=0.87), and 8.7 vs. 10 (hazard ratios 0.96, p=0.82). Projected Ctrough at cycle 3day 1 based exposure, high CD16/FcγRIIIa on peripheral immune cells, and GPC3 expression in the tumor, were all associated with prolonged progression free survival and overall survival.
CONCLUSIONS:
Codrituzumab did not show clinical benefit in this previously treated HCC population. Whether higher codrituzumab drug exposure or the use of CD16 and GPC3 as potential biomarkers would improve outcome remain unanswered questions.
LAY SUMMARY:
Codrituzumab is a manufactured antibody against a liver cancer protein called glypican-3. In this clinical trial, codrituzumab was not found be effective against liver cancer. It was suggested though that a higher dose of codrituzumab or selecting patients with high level of glypican-3 or its mediator CD16 might improve outcome.
CLINICAL TRIAL REGISTRATION:
This trial is registered at Clinicaltrials.gov (NCT01507168).
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Essai randomisé de phase II contrôlée vs placebo : étude Codrituzumab ; chez les patients déjà traités atteints d'un carcinome hépatocellulaire avancé.
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Le Codrituzumab n'a pas montré un bénéfice clinique dans cette population de patients atteints d’une CHC en deuxième ligne.
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Malheureusement.
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