Author information

• ¹Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
• ²Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
• ³Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan.
• ⁴Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.
• ⁵Department of Medicine, Mass General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
• ⁶Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany.
• ⁷Department of Medical Oncology, People's Liberation Army Cancer Center, Nanjing Bayi Hospital, Nanjing, People's Republic of China.
• ⁸Eli Lilly and Company, Indianapolis, IN, USA.
• ⁹Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
• ¹⁰Jiahui International Cancer Center, Jiahui Health, Shanghai, People's Republic of China.

Abstract

Background: Ramucirumab is indicated for patients with advanced hepatocellular carcinoma (HCC) and α-fetoprotein (AFP) ≥400 ng/mL following sorafenib. Here, we prospectively studied ramucirumab following non-sorafenib systemic therapies.

Materials and methods: This open-label, non-comparative cohort of REACH-2 enrolled patients with advanced HCC, Child-Pugh class-A liver disease, and AFP ≥400 ng/mL who had received 1-2 lines of therapy, excluding sorafenib or chemotherapy. Ramucirumab was administered 8 mg/kg intravenously Q2W. The primary endpoint was safety. Secondary endpoints were overall survival, progression-free survival, objective response rate (RECIST v1.1), time to progression, pharmacokinetics, and patient-reported outcomes. Final analysis occurred after all enrolled patients completed ≥3 treatment cycles or discontinued treatment.

Results: Between April 27, 2018, and March 29, 2021, 47 patients were treated at 21 investigative sites in Asia, Europe, and USA. The most frequently reported grade ≥3 adverse events, regardless of causality, were hypertension (11%), proteinuria (6%), hyponatremia (6%), and AST increased (6%). Two patients died from adverse events (myocardial infarction and upper gastrointestinal hemorrhage), deemed related to treatment. Median progression-free survival, time to progression, and overall survival were 1.7 months, 2.8 months, and 8.7 months, respectively. The objective response rate was 10.6% with a median duration response of 8.3 months. Median time to deterioration in FHSI-8 total score was 4.4 months.

Conclusion: Ramucirumab demonstrated consistent and meaningful clinical activity with no new safety signals following non-sorafenib therapies in patients with advanced HCC and AFP ≥400 ng/mL. This represents one of the first sequencing studies for patients with advanced HCC not treated with sorafenib.