Background: REACH was a global, multicenter, double-blind, phase 3 study evaluating the efficacy and safety of RAM as a single agent for patients (pts) with advanced HCC after prior sorafenib. Methods: Eligible intention-to-treat (ITT) population included: Child-Pugh (CP) A; advanced HCC; Barcelona Clinic Liver Cancer stage C or B refractory or not amenable to locoregional therapy; Eastern Cooperative Oncology Group performance status 0–1; prior sorafenib; and adequate hematologic and biochemical parameters. Pts were randomized 1:1 to receive RAM (8mg/kg IV) or placebo (PBO) every 2 weeks until progression, unacceptable toxicity, or death. CP B pts were enrolled initially; analyses in this population are exploratory. RAM treatment efficacy and safety data are presented for the ITT (CP A) and CP score 7 + 8 (CP B) populations, and for the pre-specified subgroup of pts with baseline alpha-fetoprotein (AFP) 3 or <400 ng/mL. Analyses compared overall survival (OS) using stratified or unstratified log-rank tests. Hazard ratios (HR) were generated using a corresponding Cox regression model. Results: The OS HR for the ITT population (RAM 283; PBO 282) was 0.866 (95%CI 0.72–1.05; p = 0.1391); median OS was 9.2m for RAM vs 7.6m for PBO. The observed safety profile of RAM in the ITT population was consistent with advanced HCC and the previously demonstrated safety profile for single-agent RAM. In ITT (CP A) pts with baseline AFP ≥400 ng/mL (RAM 119; PBO 131), OS HR was 0.674 (95%CI 0.508–0.895; p = 0.0059); median OS was 7.8m for RAM vs 4.2m for PBO. In CP B pts (RAM 39; PBO 39), OS HR was 0.998 (95%CI 0.623–1.599; p = 0.9946). In CP B pts with AFP ≥400 ng/mL, OS HR was 0.674 (0.332–1.368; p = 0.2756). The safety profile in ITT pts with baseline AFP ≥ or <400 ng/mL was consistent with the overall ITT safety population. Detailed quality-of-life (QoL) analyses and safety results will be presented. Conclusions: A statistically significant improvement in OS was not met in REACH using single-agent RAM. However, a consistent and clinically meaningful improvement in OS was observed in pts with baseline AFP levels ≥400ng/mL who received RAM, warranting further investigation. In the ITT population with baseline AFP ≥400ng/mL, a trend for delay in symptoms and performance status deterioration was observed. The safety profile of RAM in the ITT population is considered manageable, regardless of baseline AFP.
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|Data di pubblicazione:||2015|
|Titolo:||Ramucirumab (RAM) as Second-Line Treatment in Patients with Advanced Hepatocellular Carcinoma (HCC) Following First-Line Therapy with Sorafenib: Analyses from the Randomized Phase III REACH Study|
|Autori:||Barone, C.; Brandi, G.; Daniele, B.; Villa, E.; Leo, S.; Di Fabio, F.; Aprile, G.; Colombo, M.; Sobrero, A.; Giannelli, G.; Porta, C.; Cabibbo, G.; Zhu, A.; Blanc, J.; Okusaka, T.; Chau, I.; Abada, P.; Yang, L.; Pastorelli, D.|
|Digital Object Identifier (DOI):||https://doi.org/10.1093/annonc/mdv344.03|
|Appare nelle tipologie:||Articolo su rivista|
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