Characterization of Tumor Responses in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib in the Phase 3 Randomized Trial: REFLECT

Richard S Finn ¹, Shukui Qin ², Fabio Piscaglia ^3,4

¹Division of Hematology/Oncology, Department of Medicine, Geffen School of Medicine, UCLA Medical Center, Los Angeles, CA, USA.
²Director of the Chinese PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, China.
³Division of Internal Medicine, Hepatobiliary and Immunoallergic Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁴Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
⁵Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK.
⁶Princess Margaret Cancer Centre, Toronto, ON, Canada.
⁷Department of Medical Oncology, Marqués de Valdecilla University Hospital, IDIVAL, UNICAN, Santander, Spain.
⁸Medical Affairs, Eisai Inc., Nutley, NJ, USA.
⁹Biostatistics, Eisai Inc., Nutley, NJ, USA.
¹⁰Clinical Research, Eisai Inc., Nutley, NJ, USA.
¹¹Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
¹²Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan.

⁰Division of Hematology/Oncology, Department of Medicine, Geffen School of Medicine, UCLA Medical Center, Los Angeles, CA, USA.

Liver Cancer +

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October 22, 2024

View abstract on PubMed

Summary

Lenvatinib showed comparable overall survival to sorafenib in unresectable hepatocellular carcinoma. Objective response rates were higher with lenvatinib, with early and durable tumor responses observed across patient subgroups.

Area Of Science

Hepatobiliary Cancers
Oncology
Medical Imaging

Background

The REFLECT trial demonstrated lenvatinib's noninferiority to sorafenib for overall survival in unresectable hepatocellular carcinoma (uHCC).
Objective response rate (ORR) is a key efficacy endpoint, with lenvatinib showing varied ORRs based on assessment criteria (RECIST v1.1 vs. mRECIST).

Purpose Of The Study

To further characterize tumor responses to lenvatinib in patients with uHCC.
To explore the significance of objective response rate (ORR) among other outcomes in HCC treatment.

Main Methods

Efficacy was assessed in 478 patients randomly assigned to lenvatinib.
Tumor responses were evaluated by blinded independent imaging review (IIR) using both RECIST v1.1 and modified RECIST (mRECIST) criteria.
Time to response (TTR) and duration of response (DOR) were analyzed for patients achieving objective responses.

Main Results

Lenvatinib achieved an ORR of 18.8% per RECIST v1.1 and 40.6% per mRECIST.
Median TTR/DOR were 2.8 months/7.4 months (RECIST v1.1) and 1.9 months/7.3 months (mRECIST).
Responses were observed in patients with more severe baseline disease characteristics, including Child-Pugh scores and elevated alpha-fetoprotein levels.

Conclusions

Tumor responses to lenvatinib in uHCC patients occurred early and were durable.
These responses were evident even in patients with significant disease burden at baseline.
The findings support the characterization of lenvatinib's efficacy beyond overall survival, highlighting the importance of response metrics.

Keywords:

Hepatocellular carcinoma Lenvatinib Objective response