Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib

Patient-focused outcome results from the randomised phase III REACH study

Ian Chau, Markus Peck-Radosavljevic, Christophe Borg, Peter Malfertheiner, Jean Francois Seitz, Joon Oh Park, Baek Yeol Ryoo, Chia Jui Yen, Masatoshi Kudo, Ronnie Poon, Davide Pastorelli, Jean Frederic Blanc, Hyuncheol Chung, Ari D. Baron, Takuji Okusaka, L. Bowman, Zhanglin Lin Cui, Allicia C. Girvan, Paolo B. Abada, Ling Yang & 1 others Andrew X. Zhu

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalEuropean Journal of Cancer
Volume81
DOIs
Publication statusPublished - 2017 Aug 1

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Hepatocellular Carcinoma
Placebos
alpha-Fetoproteins
Quality of Life
Therapeutics
ramucirumab
sorafenib
Clinical Trials
Survival
Serum

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chau, Ian ; Peck-Radosavljevic, Markus ; Borg, Christophe ; Malfertheiner, Peter ; Seitz, Jean Francois ; Park, Joon Oh ; Ryoo, Baek Yeol ; Yen, Chia Jui ; Kudo, Masatoshi ; Poon, Ronnie ; Pastorelli, Davide ; Blanc, Jean Frederic ; Chung, Hyuncheol ; Baron, Ari D. ; Okusaka, Takuji ; Bowman, L. ; Cui, Zhanglin Lin ; Girvan, Allicia C. ; Abada, Paolo B. ; Yang, Ling ; Zhu, Andrew X. / Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib : Patient-focused outcome results from the randomised phase III REACH study. In: European Journal of Cancer. 2017 ; Vol. 81. pp. 17-25.
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abstract = "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.",
author = "Ian Chau and Markus Peck-Radosavljevic and Christophe Borg and Peter Malfertheiner and Seitz, {Jean Francois} and Park, {Joon Oh} and Ryoo, {Baek Yeol} and Yen, {Chia Jui} and Masatoshi Kudo and Ronnie Poon and Davide Pastorelli and Blanc, {Jean Frederic} and Hyuncheol Chung and Baron, {Ari D.} and Takuji Okusaka and L. Bowman and Cui, {Zhanglin Lin} and Girvan, {Allicia C.} and Abada, {Paolo B.} and Ling Yang and Zhu, {Andrew X.}",
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Chau, I, Peck-Radosavljevic, M, Borg, C, Malfertheiner, P, Seitz, JF, Park, JO, Ryoo, BY, Yen, CJ, Kudo, M, Poon, R, Pastorelli, D, Blanc, JF, Chung, H, Baron, AD, Okusaka, T, Bowman, L, Cui, ZL, Girvan, AC, Abada, PB, Yang, L & Zhu, AX 2017, 'Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib: Patient-focused outcome results from the randomised phase III REACH study', European Journal of Cancer, vol. 81, pp. 17-25. https://doi.org/10.1016/j.ejca.2017.05.001

Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib : Patient-focused outcome results from the randomised phase III REACH study. / Chau, Ian; Peck-Radosavljevic, Markus; Borg, Christophe; Malfertheiner, Peter; Seitz, Jean Francois; Park, Joon Oh; Ryoo, Baek Yeol; Yen, Chia Jui; Kudo, Masatoshi; Poon, Ronnie; Pastorelli, Davide; Blanc, Jean Frederic; Chung, Hyuncheol; Baron, Ari D.; Okusaka, Takuji; Bowman, L.; Cui, Zhanglin Lin; Girvan, Allicia C.; Abada, Paolo B.; Yang, Ling; Zhu, Andrew X.

In: European Journal of Cancer, Vol. 81, 01.08.2017, p. 17-25.

Research output: Contribution to journalArticle

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, Hyuncheol

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.

PY - 2017/8/1

Y1 - 2017/8/1

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.

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