Real-world Outcomes for Patients with HCC Receiving Lenvatinib After IO

Amit Mahipal, MD, University Hospitals Seidman Cancer Center, and Richard S. Finn, MD, University of California, Los Angeles, discuss a recent study on real-world outcomes for patients with advanced hepatocellular carcinoma receiving lenvatinib following immunotherapy.

Dr. Finn: I’m keen to learn more about your recently published paper in Cancers on outcomes of patients with advanced hepatocellular carcinoma receiving lenvatinib following immunotherapy—a real-world evidence study. This topic holds significant clinical relevance in the modern age. As your paper acknowledges, the historical frontline role for advanced patients was occupied by the tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib in liver cancer. However, with the advent of immunotherapy-based combinations like atezolizumab/bevacizumab or durvalumab/tremelimumab in the frontline setting, the data supporting drugs like lenvatinib needs reevaluation. The REFLECT study, the pivotal study for lenvatinib, was conducted versus sorafenib before the use of immunotherapy in the frontline, and now there’s a need for data supporting the continued use of these drugs in the modern era of liver cancer management. Could you provide some background on this study and how it addresses this question?

Dr. Mahipal: The treatment landscape for hepatocellular cancer has undergone significant changes in recent years, thanks in part to pivotal clinical trials. TKIs were once the first- and second-line treatments. Now, with immunotherapy taking the lead in the first-line, using drugs like atezolizumab/bevacizumab or durvalumab/tremelimumab, the response of patients on TKIs after receiving immunotherapy remains uncertain. While lenvatinib and sorafenib are commonly used based on previous data, including the REFLECT study, which predates immunotherapy in the frontline, there’s a gap in understanding how these TKIs perform in the modern era. Our study aimed to fill this gap by examining real-world outcomes for patients receiving lenvatinib after progressing on immunotherapy. Although lacking clinical trial data, this approach is routinely employed in clinical practice. We sought to understand if the outcomes align with expectations and if there are variations in the rate and nature of progression.

Expanding on the trial, we conducted the study at Mayo Clinic across three sites—Minnesota, Arizona, and Florida. We analyzed outcomes for 53 patients who received lenvatinib after progressing on immunotherapy, with over 85% being second-line recipients. Notably, the median progression-free survival (PFS) was approximately 3.7 months, and the median overall survival (OS) was around 12.8 months. When focusing on patients with Child-Pugh A status, the median OS increased to about 14 months, and the median PFS rose to 5.2 months. These findings align with expectations and are consistent with the REFLECT trial results. It’s crucial to note that this real-world study, conducted in a broad tertiary care center with diverse patient referrals, may differ from a randomized phase 3 clinical trial.

Dr. Finn: Indeed, it’s essential to recognize the differences between real-world evidence and controlled phase 3 studies. Survival data remains objective, but factors like PFS depend on imaging frequency and interpretation. Your study also highlights a noteworthy objective response rate (ORR).

Dr. Mahipal: Absolutely. While PFS and objective response rate may be somewhat subjective, we ensured consistency in our internal review for the ORR. However, the caveat with PFS lies in the variability of scan intervals based on patient conditions and toxicities. This inconsistency is an inherent challenge compared to the more standardized approach of a randomized control trial. I fully agree with your assessment.

View their further comments on Safety Considerations and Prognostic Factors for Patients with HCC Receiving Lenvatinib After IO.