Ian Chau1, Markus Peck-Radosavljevic2, Christophe Borg3, Peter Malfertheiner4, Jean Francois Seitz5, Joon Oh Park6, Baek-Yeol Ryoo7, Chia-Jui Yen8, Masatoshi Kudo9, Ronnie Poon10, Davide Pastorelli11, Jean-Frederic Blanc12, Hyun Cheol Chung13, Ari D Baron14, Takuji Okusaka15, L Bowman16, Zhanglin Lin Cui16, Allicia C Girvan16, Paolo B Abada16, Ling Yang17, Andrew X Zhu18. 1. Royal Marsden Hospital, London and Surrey, United Kingdom. Electronic address: ian.chau@rmh.nhs.uk. 2. Allgemeines Krankenhaus Wien, Vienna and Klinkum Klagenfurt am Wörthersee, Klagenfurt, Austria. 3. Hospital Jean Minjoz, Besançon, France. 4. Universitätsklinikum Magdeburg, Magdeburg, Germany. 5. Hôpital La Timone, Aix-Marseille University, Marseille, France. 6. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 7. Asan Medical Center, Seoul, Republic of Korea. 8. National Cheng Kung University Hospital, Tainan, Taiwan. 9. Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. 10. The University of Hong Kong, Hong Kong. 11. Istituto Oncologico Veneto IRCCS, Padova, Italy. 12. Hepato-Gastroenterology and Digestive Oncology Unit, Centre Medico-chirurgical Magellan, CHU Bordeaux, France. 13. Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea. 14. Sutter Health California Pacific Medical Center, San Francisco, CA, USA. 15. National Cancer Center Hospital, Tokyo, Japan. 16. Eli Lilly and Company, Indianapolis, IN, USA. 17. Eli Lilly and Company, Bridgewater, NJ, USA. 18. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
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 priorsorafenib. 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 toramucirumab 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.
RCT Entities:
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.
Authors: Cyrill Wehling; Daniel Hornuss; Pasquale Schneider; Christoph Springfeld; Katrin Hoffmann; De-Hua Chang; Patrick Naumann; Markus Mieth; Thomas Longerich; Clemens Kratochwil; Arianeb Mehrabi; Annika Gauss; Karl Heinz Weiss; Jan Pfeiffenberger Journal: J Cancer Res Clin Oncol Date: 2019-08-19 Impact factor: 4.553
Authors: B M Meyers; J Knox; R Cosby; J R Beecroft; K K W Chan; N Coburn; J Feld; D Jonker; A Mahmud; J Ringash Journal: Curr Oncol Date: 2020-05-01 Impact factor: 3.677