TY - JOUR
T1 - Safety and Preliminary Efficacy of Ramucirumab in Combination with FOLFOX4 in Patients with Advanced Hepatocellular Carcinoma
T2 - A Nonrandomized, Open-Label, Phase Ib Study
AU - Lin, Chia Chi
AU - Yang, Tsai Sheng
AU - Yen, Chia Jui
AU - Cheng, Rebecca
AU - Liu, Junjun
AU - Hsu, Chiun
N1 - Funding Information:
The authors thank Wanli Zhang and Chengwei Li from Eli Lilly and Company for analysis and interpretation of data. The authors also thank Rakesh Ojha, Ph.D., from Syneos Health, for medical writing support, as well as Christopher Glaser Jr. and Cynthia Rae Abbott from Syneos Health for editorial support in the preparation of the CTR. The authors are indebted to the patients who participated in this study and to their families. This study was sponsored by Eli Lilly and Company.
Publisher Copyright:
© AlphaMed Press; the data published online to support this summary are the property of the authors.
PY - 2020/12
Y1 - 2020/12
N2 - Lessons Learned: The combination of ramucirumab (8 mg/kg intravenous, day 1 every 2 weeks) and FOLFOX4 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC) was not sufficiently tolerated. Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with HCC. Dose modification and patient selection should be considered for the future development of ramucirumab plus FOLFOX chemotherapy for advanced HCC. Background: The objective of this study was to investigate the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of ramucirumab plus FOLFOX4 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC). Methods: Patients received ramucirumab (8 mg/kg) intravenously (IV) on day 1, followed by FOLFOX4 (oxaliplatin 85 mg/m2 IV on day 1, folinic acid 200 mg/m2 IV, bolus fluorouracil [5-FU] 400 mg/m2, and a continuous infusion of 5-FU 600 mg/m2 over 22 hours, on days 1 and 2) every 2 weeks. The primary endpoint was to assess the safety and tolerability of the combination therapy. Results: Eight patients (6 men, 2 women) were treated; all eight patients experienced at least one treatment-emergent adverse event (TEAE) of grade ≥3. Dose-limiting toxicities occurred in three patients (37.5%): hepatic hemorrhage (grade 4), blood bilirubin increased (grade 3), and febrile neutropenia (grade 3). Two patients discontinued study because of hepatic hemorrhage (grade 4) and blood bilirubin increase (grade 3). Six deaths occurred due to progressive disease, and no deaths due to TEAEs. Conclusion: There were no unexpected safety findings with ramucirumab plus FOLFOX4 based on the known safety and toxicity of this regimen. The combination was not sufficiently tolerated in patients with advanced HCC at the specified dose and schedule.
AB - Lessons Learned: The combination of ramucirumab (8 mg/kg intravenous, day 1 every 2 weeks) and FOLFOX4 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC) was not sufficiently tolerated. Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with HCC. Dose modification and patient selection should be considered for the future development of ramucirumab plus FOLFOX chemotherapy for advanced HCC. Background: The objective of this study was to investigate the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of ramucirumab plus FOLFOX4 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC). Methods: Patients received ramucirumab (8 mg/kg) intravenously (IV) on day 1, followed by FOLFOX4 (oxaliplatin 85 mg/m2 IV on day 1, folinic acid 200 mg/m2 IV, bolus fluorouracil [5-FU] 400 mg/m2, and a continuous infusion of 5-FU 600 mg/m2 over 22 hours, on days 1 and 2) every 2 weeks. The primary endpoint was to assess the safety and tolerability of the combination therapy. Results: Eight patients (6 men, 2 women) were treated; all eight patients experienced at least one treatment-emergent adverse event (TEAE) of grade ≥3. Dose-limiting toxicities occurred in three patients (37.5%): hepatic hemorrhage (grade 4), blood bilirubin increased (grade 3), and febrile neutropenia (grade 3). Two patients discontinued study because of hepatic hemorrhage (grade 4) and blood bilirubin increase (grade 3). Six deaths occurred due to progressive disease, and no deaths due to TEAEs. Conclusion: There were no unexpected safety findings with ramucirumab plus FOLFOX4 based on the known safety and toxicity of this regimen. The combination was not sufficiently tolerated in patients with advanced HCC at the specified dose and schedule.
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U2 - 10.1002/onco.13550
DO - 10.1002/onco.13550
M3 - Article
C2 - 33017497
AN - SCOPUS:85094950195
SN - 1083-7159
VL - 25
SP - e1921-e1929
JO - Oncologist
JF - Oncologist
IS - 12
ER -