Richard S. Finn, MD

Richard S. Finn, MD, professor of medicine in the division of hematology/oncology, department of medicine at the Geffen School of Medicine at UCLA, discusses key takeaways of the LEAP-002 trial (NCT03713593) of frontline pembrolizumab (Keytruda) and lenvatinib (Lenvima) for hepatocellular carcinoma (HCC).

Results of the phase 3 study presented at the 2022 European Society for Medical Oncology Congress showed a 21-month median overall survival (OS) for the pembrolizumab/lenvatinib combination; however, the comparator arm of lenvatinib alone had a median OS of 19 months, with the difference being insufficient to show survival benefit of the combination. Finn notes that lenvatinib alone showed an impressive OS, though this was in a population that excluded those with a main portal vein invasion.

According to Finn, the HIMALAYA study (NCT03298451), which recently led to the approval of durvalumab (Imfinzi) plus tremelimumab (Imjudo), had a median OS of around 16 months. Additionally, the IMbrave150 study (NCT03434379) of atezolizumab (Tecentriq) and bevacizumab (Avastin) reached a median OS of over 19 months in a higher-risk population, including main portal vein invasion. Despite not reaching statistically significant survival benefit when combined with pembrolizumab, Finn says the comparator arm’s outcomes indicates that lenvatinib has an important role in HCC. 

Pembrolizumab and lenvatinib are also under investigation in the LEAP-012 trial (NCT04246177) in combination with transarterial chemoembolization (TACE) in patients with incurable nonmetastatic HCC, which could show a different role for this combination.

A few things we learned from this study: lenvatinib and pembrolizumab are safe. It's active in liver cancer but was not statistically better than lenvatinib alone. What we did learn is that lenvatinib alone is a very active regimen for patients in the frontline setting, giving an OS of 19 months. It's important to note that the 19 months is in a population that did not have a main portal vein invasion.

If we look at other phase 3 studies in that space, [these results] compare to the HIMALAYA study where durvalumab and tremelimumab had a survival of around 16 months. But when the IMbrave150 study of atezolizumab and bevacizumab reports a survival of over 19 months; that is in a higher-risk population, i.e, patients who did have, or included, main portal vein invasion.

 Lenvatinib is an important option for our patients with advanced liver cancer. It's important to keep that in mind. [This combination] is still being evaluated in another phase 3 study of lenvatinib and pembrolizumab plus TACE for patients with intermediate liver cancer as well. That's a phase 3 study of that combination versus TACE alone.

Videos

Richard S. Finn, MD, discusses key takeaways of the LEAP-002 trial of frontline pembrolizumab and lenvatinib for hepatocellular carcinoma.

Key Takeaways of the Survival Outcomes From the LEAP-002 Trial for HCC

Richard S. Finn, MD, an assistant professor of clinical medicine at the Geffen School of Medicine at the University of California, Los Angeles (UCLA), and director of the Signal Transduction and Therapeutics Program at the Jonsson Comprehensive Cancer Center at UCLA, discusses the real-world findings from the REFINE study, which is exploring the outcomes of patients with unresectable hepatocellular carcinoma (HCC) who received treatment with regorafenib (Stivarga) compared with those in the clinical setting who were treated on the phase 3 RESORCE study.

In the real-world findings, just more than half of the doctors start patients on the full dose as prescribed, while others started patients at 80 or 120 mg per day, Finn says. Regardless, the efficacy and side effect profiles were similar between those treated in the real world versus the clinical trial setting.

Finn says that in terms of the length of time patients received regorafenib, the findings were comparable at about 4 months. Dose reductions were fairly common, regardless of the dose.

When investigators looked at why doctors used a lower dose, there seemed to be a relation with their prior dose of sorafenib (Nexavar). In the RESORCE study, patients received a fixed dose of regorafenib, and there was no effect on the efficacy and tolerability of the drug. Patients who were on sorafenib for a shorter period of time, they still received a similar magnitude of benefit with regorafenib, and vice versa, Finn says.

Richard S. Finn, MD, discusses the real-world findings from the REFINE study of patients with unresectable hepatocellular carcinoma who received treatment with regorafenib.

Real-World Findings in REFINE Study Support Use of Regorafenib in HCC

Richard S. Finn, MD, professor of Clinical Medicine Division of Hematology/Oncology, UCLA David Geffen School of Medicine, University of California, Los Angeles, discusses the considerations he makes when selecting frontline treatment for patients with advanced hepatocellular carcinoma (HCC).

Both sorafenib (Nexavar) and lenvatinib (Lenvima) have been approved by the FDA for the treatment of patients with advanced HCC in the frontline setting. The REFLECT trial that compared the 2 agents was a noninferiority trial, so Finn says neither agent is superior to the other.

According to both traditional and modified RECIST criteria, lenvatinib has a higher response rate, but no drug has ever been able to beat the survival rates seen with sorafenib, Finn notes. Data from the REFLECT study showed that if a patient has a response with either agent, that could provide a survival of 22 months, or even more in select patient populations.

Richard S. Finn, MD, discusses the considerations he makes when selecting frontline treatment for patients with advanced hepatocellular carcinoma.

Comparing Sorafenib and Lenvatinib for the Frontline Treatment of Advanced HCC

Richard S. Finn, MD, assistant professor of medicine, Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine, University of California, Los Angeles, discusses&nbsp;advances in the development of CDK4/6 inhibitors for the treatment of hormone receptor (HR)-positive breast cancer. &nbsp; &nbsp;

Latest Advances in the Development of CDK4/6 Inhibitors in HR+ Breast Cancer

Richard S. Finn, MD, an associate professor of Medicine at the UCLA David Geffen School of Medicine, discusses the role of immunotherapy in the treatment of liver cancer.

The Role of Immunotherapy in Liver Cancer

Richard S. Finn, MD, associate professor of medicine, Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, discusses the use of tivantinib and regorafenib for the treatment of patients with liver cancer.

Tivantinib is in phase III development for liver cancer

A phase II study comparing tivantinib to placebo showed no dramatic benefit in all-comers

An analysis showed high MET expression was associated with worse prognosis, and high MET patients saw benefit from tivantinib versus low MET

Regorafenib has shown activity in colorectal cancer and GIST

A phase II study of regorafenib demonstrated provocative survival data for patients who have progressed on sorafenib

Richard S. Finn, MD | Authors

Articles

Key Takeaways of the Survival Outcomes From the LEAP-002 Trial for HCC

Real-World Findings in REFINE Study Support Use of Regorafenib in HCC

Comparing Sorafenib and Lenvatinib for the Frontline Treatment of Advanced HCC

Latest Advances in the Development of CDK4/6 Inhibitors in HR+ Breast Cancer

The Role of Immunotherapy in Liver Cancer

Tivantinib and Regorafenib for the Treatment of Liver Cancer