A randomized, double-blind, placebo-controlled phase II study to assess the efficacy and safety of mapatumumab with sorafenib in patients with advanced hepatocellular carcinoma
Mené sur 101 patients atteints d'un carcinome hépatocellulaire de stade avancé, cet essai randomisé de phase II évalue l'efficacité, du point de vue du délai avant progression, et la toxicité de l'ajout du mapatumumab au sorafénib
Background This randomized, double-blind, placebo-controlled, phase II study evaluated the efficacy and safety of mapatumumab (a human agonistic monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 1) in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods Patients with advanced HCC (stratified by Barcelona Clinic Liver Cancer stage and Eastern Cooperative Oncology Group performance status), were randomized 1:1 to receive sorafenib (400 mg, twice daily per 21-day cycle) and either placebo (placebo-sorafenib arm) or mapatumumab (30 mg/kg on Day 1 per 21-day cycle; mapatumumab-sorafenib arm). The primary endpoint was time to (radiologic) progression (TTP), assessed by blinded independent central review. Key secondary endpoints included progression-free survival, overall survival, and objective response. Results In total, 101 patients were randomized (placebo-sorafenib arm: N=51; mapatumumab-sorafenib arm: N=50). There was no significant difference in median TTP between both arms (5.6 vs 4.1 months, respectively; adjusted hazard ratio [one-sided 90% confidence interval]: 1.192 [0, 1.737]). No mapatumumab-related benefit was identified when TTP was evaluated in the stratified subgroups. The addition of mapatumumab to sorafenib did not demonstrate improvement in the secondary efficacy endpoints. The reported frequency of adverse events (AEs) and serious AEs was comparable in both treatment arms. Conclusions The addition of mapatumumab to sorafenib did not improve TTP or other efficacy endpoints, nor did it substantially change the toxicity profile of sorafenib in patients with advanced HCC. Based on these results, further development of the combination of mapatumumab and sorafenib in HCC is not planned.
Annals of Oncology 2016