TY - JOUR
T1 - Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib
T2 - Patient-focused outcome results from the randomised phase III REACH study
AU - Chau, Ian
AU - Peck-Radosavljevic, Markus
AU - Borg, Christophe
AU - Malfertheiner, Peter
AU - Seitz, Jean Francois
AU - Park, Joon Oh
AU - Ryoo, Baek-Yeol
AU - Yen, Chia-Jui
AU - Kudo, Masatoshi
AU - Poon, Ronnie
AU - Pastorelli, Davide
AU - Blanc, Jean-Frederic
AU - Chung, Hyun Cheol
AU - Baron, Ari D
AU - Okusaka, Takuji
AU - Bowman, L
AU - Cui, Zhanglin Lin
AU - Girvan, Allicia C
AU - Abada, Paolo B
AU - Yang, Ling
AU - Zhu, Andrew X
N1 - Copyright © 2017 Elsevier Ltd. All rights reserved.
PY - 2017/8
Y1 - 2017/8
N2 - PURPOSE: To report patient-focused outcomes as measured by quality of life (QoL) and performance status (PS) in REACH, a phase III placebo-controlled randomised study, assessing ramucirumab in advanced hepatocellular carcinoma (HCC) patients who received prior sorafenib.METHODS: Eligible patients had advanced HCC, Child-Pugh A, PS 0 or 1 and prior sorafenib. Patients received ramucirumab (8 mg/kg) or placebo (1:1) on day 1 of a 2-week cycle. QoL was assessed by FACT Hepatobiliary Symptom Index (FHSI)-8 and EuroQoL (EQ-5D) at baseline; cycles 4, 10, and 16; and end of treatment. PS was assessed at baseline, each cycle, and end of treatment. Deterioration in FHSI-8 was defined as a ≥3-point decrease from baseline and PS deterioration was defined as a change of ≥2. Both intention-to-treat and pre-specified subgroup of patients with baseline serum alpha-fetoprotein (AFP) ≥400 ng/mL were assessed.RESULTS: There were 565 patients randomised to ramucirumab and placebo. Compliance with FHSI and EQ-5D was high and similar between groups. In the ITT population, deterioration in FHSI-8, EQ-5D, and PS was similar between ramucirumab and placebo. In patients with baseline AFP ≥400 ng/mL, ramucirumab significantly reduced deterioration in FHSI-8 at the end of treatment compared with placebo (P = 0.0381), and there was a trend towards a delay in the deterioration of symptoms in FHSI-8 (HR 0.690; P = 0.054) and PS (HR 0.642; P = 0.057) in favour of ramucirumab.CONCLUSIONS: We report one of the most comprehensive data sets of QoL and symptom burden in patients undergoing systemic therapy for advanced HCC. Ramucirumab was associated with no worsening of QoL. In patients with baseline AFP ≥400 ng/mL, the significant survival benefit observed in patients treated with ramucirumab was coupled with a trend in patient-focused outcome benefits.CLINICAL TRIAL REGISTRATION: NCT01140347.
AB - PURPOSE: To report patient-focused outcomes as measured by quality of life (QoL) and performance status (PS) in REACH, a phase III placebo-controlled randomised study, assessing ramucirumab in advanced hepatocellular carcinoma (HCC) patients who received prior sorafenib.METHODS: Eligible patients had advanced HCC, Child-Pugh A, PS 0 or 1 and prior sorafenib. Patients received ramucirumab (8 mg/kg) or placebo (1:1) on day 1 of a 2-week cycle. QoL was assessed by FACT Hepatobiliary Symptom Index (FHSI)-8 and EuroQoL (EQ-5D) at baseline; cycles 4, 10, and 16; and end of treatment. PS was assessed at baseline, each cycle, and end of treatment. Deterioration in FHSI-8 was defined as a ≥3-point decrease from baseline and PS deterioration was defined as a change of ≥2. Both intention-to-treat and pre-specified subgroup of patients with baseline serum alpha-fetoprotein (AFP) ≥400 ng/mL were assessed.RESULTS: There were 565 patients randomised to ramucirumab and placebo. Compliance with FHSI and EQ-5D was high and similar between groups. In the ITT population, deterioration in FHSI-8, EQ-5D, and PS was similar between ramucirumab and placebo. In patients with baseline AFP ≥400 ng/mL, ramucirumab significantly reduced deterioration in FHSI-8 at the end of treatment compared with placebo (P = 0.0381), and there was a trend towards a delay in the deterioration of symptoms in FHSI-8 (HR 0.690; P = 0.054) and PS (HR 0.642; P = 0.057) in favour of ramucirumab.CONCLUSIONS: We report one of the most comprehensive data sets of QoL and symptom burden in patients undergoing systemic therapy for advanced HCC. Ramucirumab was associated with no worsening of QoL. In patients with baseline AFP ≥400 ng/mL, the significant survival benefit observed in patients treated with ramucirumab was coupled with a trend in patient-focused outcome benefits.CLINICAL TRIAL REGISTRATION: NCT01140347.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antibodies, Monoclonal
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Carcinoma, Hepatocellular
KW - Disease-Free Survival
KW - Double-Blind Method
KW - Female
KW - Humans
KW - Kaplan-Meier Estimate
KW - Liver Neoplasms
KW - Male
KW - Middle Aged
KW - Niacinamide
KW - Phenylurea Compounds
KW - Quality of Life
KW - Clinical Trial, Phase III
KW - Journal Article
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.ejca.2017.05.001
DO - 10.1016/j.ejca.2017.05.001
M3 - Article
C2 - 28591675
VL - 81
SP - 17
EP - 25
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -