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; Hyun Cheol Chung; Ari D Baron; Takuji Okusaka; L Bowman; Zhanglin Lin Cui; Allicia C Girvan; Paolo B Abada; Ling Yang; Andrew X Zhu

doi: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

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, Hyun Cheol Chung, Ari D Baron, Takuji Okusaka, L Bowman, Zhanglin Lin Cui, Allicia C Girvan, Paolo B Abada, Ling YangAndrew X Zhu

Istituto Oncologico Veneto

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	17-25
Number of pages	9
Journal	European Journal of Cancer
Volume	81
DOIs	https://doi.org/10.1016/j.ejca.2017.05.001
Publication status	Published - Aug 2017

Keywords

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Hepatocellular
Disease-Free Survival
Double-Blind Method
Female
Humans
Kaplan-Meier Estimate
Liver Neoplasms
Male
Middle Aged
Niacinamide
Phenylurea Compounds
Quality of Life
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

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Chau, I., Peck-Radosavljevic, M., Borg, C., Malfertheiner, P., Seitz, J. F., Park, J. O., Ryoo, B-Y., Yen, C-J., Kudo, M., Poon, R., Pastorelli, D., Blanc, J-F., Chung, H. C., Baron, A. D., Okusaka, T., Bowman, L., Cui, Z. L., Girvan, A. C., Abada, P. B., ... Zhu, A. X. (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, 81, 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, Hyun Cheol; 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, 08.2017, p. 17-25.

Research output: Contribution to journal › Article › peer-review

Chau, I, Peck-Radosavljevic, M, Borg, C, Malfertheiner, P, Seitz, JF, Park, JO, Ryoo, B-Y, Yen, C-J, Kudo, M, Poon, R, Pastorelli, D, Blanc, J-F, Chung, HC, 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

Chau I, Peck-Radosavljevic M, Borg C, Malfertheiner P, Seitz JF, Park JO et al. 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. 2017 Aug;81:17-25. https://doi.org/10.1016/j.ejca.2017.05.001

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, Hyun Cheol ; 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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title = "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",

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.",

keywords = "Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Hepatocellular, Disease-Free Survival, Double-Blind Method, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms, Male, Middle Aged, Niacinamide, Phenylurea Compounds, Quality of Life, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",

author = "Ian Chau and Markus Peck-Radosavljevic and Christophe Borg and Peter Malfertheiner and Seitz, {Jean Francois} and Park, {Joon Oh} and Baek-Yeol Ryoo and Chia-Jui Yen and Masatoshi Kudo and Ronnie Poon and Davide Pastorelli and Jean-Frederic Blanc and Chung, {Hyun Cheol} 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}",

year = "2017",

month = aug,

doi = "10.1016/j.ejca.2017.05.001",

language = "English",

volume = "81",

pages = "17--25",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd",

}

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

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 -