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

Andrew X. Zhu*, Ryan D. Nipp, Richard S. Finn, Peter R. Galle, Josep M. Llovet, Jean Frederic Blanc, Takuji Okusaka, Ian Chau, David Cella, Allicia Girvan, Jonathon Gable, Lee Bowman, Chunxiao Wang, Yanzhi Hsu, Paolo B. Abada, Masatoshi Kudo

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere000797
JournalESMO Open
Volume5
Issue number4
DOIs
StatePublished - Aug 18 2020

Keywords

  • Hepatocellular carcinoma
  • Patient-reported outcomes
  • Quality of life
  • Ramucirumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Zhu, A. X., Nipp, R. D., Finn, R. S., Galle, P. R., Llovet, J. M., Blanc, J. F., Okusaka, T., Chau, I., Cella, D., Girvan, A., Gable, J., Bowman, L., Wang, C., Hsu, Y., Abada, P. B., & Kudo, M. (2020). Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: Patient-reported outcomes across two randomised clinical trials. ESMO Open, 5(4), [e000797]. https://doi.org/10.1136/esmoopen-2020-000797