Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: patient-reported outcomes across two randomised clinical trials

ESMO Open

article

Andrew X. Zhu¹  Ryan D. Nipp¹  Richard S. Finn³  Peter R. Galle⁴  Josep M. Llovet⁵  Jean-Frederic Blanc⁷  Takuji Okusaka⁸  Ian Chau⁹  David Cella^1,10  Allicia Girvan^1,11  Jonathon Gable^1,11  Lee Bowman^1,11  Chunxiao Wang^1,11  Yanzhi Hsu^1,12  Paolo B. Abada^1,11  Masatoshi Kudo^1,13 

[1] Harvard Medical School, Massachusetts General Hospital;Jiahui International Cancer Center, Jiahui International Hospital;Division of Hematology/Oncology, Geffen School of Medicine, University of California-Los Angeles Medical Center;First Department of Internal Medicine, University Medical Center Mainz;Translational Research Lab in Hepatic Oncology, Liver Unit, Institut d"Investigacions Biomediques August Pi i Sunyer;Mount Sinai Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai;Department of Hepatogastroenterology and Medical Oncology, CHU de Bordeaux Hôpital Haut-Lévêque;Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital;Department of Medicine, Royal Marsden Hospital;Robert H. Lurie Comprehensive Cancer Center, Northwestern University;Eli Lilly and Company;TG Therapeutics;Gastroenterology and Hepatology, Kindai University

关键词: hepatocellular carcinoma;    ramucirumab;    patient-reported outcomes;    quality of life;   

DOI  :  10.1136/esmoopen-2020-000797

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Symptoms of advanced hepatocellular carcinoma (HCC) represent a substantial burden for the patient and are important endpoints to assess when evaluating treatment. Patient-reported outcomes were evaluated in subjects with advanced HCC and baseline alpha-fetoprotein (AFP) ≥400 ng/mL treated with second-line ramucirumab.Patients and methods Patients with AFP≥400 ng/mL enrolled in the REACH or REACH-2 phase 3 studies were used in this analysis. Eligible patients had advanced HCC, Child-Pugh A, Eastern Cooperative Oncology Group performance status 0/1 and prior sorafenib. Patients received ramucirumab 8 mg/kg or placebo once every 2 weeks. Disease-related symptoms and health-related quality of life (HRQoL) were assessed with the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index (FHSI)-8 and EuroQoL-5-Dimensions (EQ-5D) instruments, respectively. Time to deterioration (TTD) (≥3-point decrease in FHSI-8 total score;≥0.06-point decrease in EQ-5D score, from randomisation to first date of deterioration) was determined using Kaplan-Meier estimation and the Cox proportional hazards model. Both separate and pooled analyses for REACH AFP≥400 ng/mL and REACH-2 patients were conducted.Results In the pooled population with AFP ≥400 ng/mL (n=542; ramucirumab, n=316; placebo, n=226), median TTD in FHSI-8 total score was prolonged with ramucirumab relative to placebo (3.3 vs 1.9 months; HR 0.725; (95% CI 0.559 to 0.941); p=0.0152), including significant differences in back pain (0.668; (0.497 to 0.899); p=0.0044), weight loss (0.699; (0.505 to 0.969); p=0.0231) and pain (0.769; (0.588 to 1.005); p=0.0248) symptoms. TTD in EQ-5D score was not significantly different between ramucirumab and placebo groups (median 2.9 vs 1.9 months). Results in the individual trials were consistent with these findings.Conclusions Ramucirumab in second-line treatment of advanced HCC demonstrates consistent benefit in the delay of deterioration in disease-related symptoms with no worsening of HRQoL. Taken with previously demonstrated ramucirumab-driven survival benefits in this setting, these data may inform patient–clinician discussions about the benefit–risk profile of this therapy.Trial registration number NCT01140347; NCT02435433, NCT02435433.

【 授权许可】

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