Lenvatinib Yields Promising Results in Unresectable HCC

Kaoru Tsuchiya, MD

Tyrosine kinase inhibitor (TKI) lenvatinib (Lenvima) demonstrated similar efficacy in patients with hepatocellular carcinoma (HCC) in real world practice in Japan compared with the phase III clinical trial, despite the inclusion of elderly patients with lower body weight, according to a retrospective analysis presented at the 2020 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium.

Single-agent lenvatinib was approved in Japan in March 2018. Investigators of the nationwide multicenter study assessed the safety and efficacy of results from a larger sample size cohort in real world practice. Overall, 116 patients with unresectable HCC who received the therapyin Japan were registered. Tumors were assessed with RECIST 1.1 and modified RECIST (mRECIST) criteria, which used CT or MRI scans within 4 to 8 weeks of treatment and every 6 to 8 weeks thereafter.

Of the 116 patients, 106 were Child-Pugh A (91.4%), and 73 patients were BCLC C (62.9%). Following frontline sorafenib (Nexavar) therapy, 28 patients received lenvatinib in the second-line setting (24.1%) and 17 patients received the drug in the third-line after second-line regorafenib (14.7%). The median time for observation was 2.5 months, and 1 patient died from progression of disease.

Forty-nine patients (42.2%) were evaluated at weeks 4 to 8. mRECIST criteria determined that 3 patients (6.1%) experienced a complete response (CR), 14 patients (28.6%) had a partial response (PR), 23 patients (46.9%) had stable disease (SD), and 6 patients (12.2%) had progressive disease (PD).

In the 3 patients who achieved a CR, target lesions of the liver demonstrated PR, although bone metastases had progressed. The objective response rate (ORR) was 34.7% in the overall population, whereas the disease control rate (DCR) was 81.6%. The ORR was 34.6% in patients who were TKI-naïve (n = 26), and the DCR was 80.8%. The ORR in patients who had received a prior TKI therapy (n = 23) was 34.8%, and the DCR was 82.6%.

Adverse events (AEs) were graded based on the CTCAE 4.0. The most common AEs of any grade were hypertension (52.0%), diarrhea (32.1%), decreased appetite (63.5%), and fatigue (49.4%). Additionally, 28% of patients experienced hand-foot skin reaction.

In an interview withTargeted Oncology,Kaoru Tsuchiya, MD, of Musashino Red Cross Hospital, Tokyo, Japan, discussed the results of the real-world study of lenvatinib in patients with unresectable HCC that are being presented at the 2020 ASCO GI Cancers Symposium.

TARGETED ONCOLOGY: What is the current treatment for patients with unresectable HCC?

We can use many new agents now, including TKIs like lenvatinib. In other countries, you can use immunotherapies, including checkpoint inhibitors, in patients with unresectable HCC. We can use many agents for our patients with unresectable disease.

TARGETED ONCOLOGY: What was the rationale for your study, and how was it designed?

In our study, we focused on the patients with intermediate HCC. These patients are candidates for TACE [transarterial chemoembolization], but as many doctors know, TACE is not as effective for all patients, especially patients beyond second-line therapy. In this study, we focused on the patients with intermediate HCC. We evaluated the efficacy and safety of lenvatinib for these patients.

The study at my institution was conducted at 22 Japanese hospitals. We collected data from 280 patients treated with lenvatinib. There were 116 patients with intermediate HCC, and we analyzed the efficacy and safety in these patients.

TARGETED ONCOLOGY: What were the results from this study?

The median survival of the patients with unresectable HCC treated with lenvatinib was not reached, especially in the patients with excellent tumor function. Excellent tumor function means the risk score is 1 or a modified risk score of 2a in such patients. The PFS [progression-free survival] was about 14 months. We think the outcome in patients with such excellent liver function and a Child-Pugh score of B [demonstrates that] lenvatinib is very effective in this space.

TARGETED ONCOLOGY: In terms of safety, how well tolerated was lenvatinib in this patient population?

In regard to the safety of lenvatinib in patients with intermediate HCC, the safety profile was similar to the patients with advanced disease. We performed additional TACE during lenvatinib therapy, and there were no severe AEs [adverse events], even with the addition of TACE, during the lenvatinib therapy.

TARGETED ONCOLOGY: How do your findings elucidate the best patient to receive lenvatinib?

We know the outcomes are not so familiar, and for the doctors in other countries, including Western countries, maybe the concept is not so easy to understand. I think some doctors are using lenvatinib in patients with intermediate HCC, but some doctors think it’s too much. We [can] carefully select which patients are the best candidates to receive lenvatinib even though the HCC stage is not advanced. We tried to make clear which patients are good candidates for lenvatinib therapy, especially in patients with unresectable HCC.

TARGETED ONCOLOGY: Where should lenvatinib be sequenced in this patient population?

Originally, the phase II clinical trial of lenvatinib was only for patients as a frontline therapy, but in Japan, we can use lenvatinib as a second-line or third-line as well. We think, especially in patients with intermediate BCLC [Barcelona clinic liver cancer] HCC, lenvatinib should be used as first-line because the outcomes in these patients was excellent. PFS was about 14 months, so we think lenvatinib should be used as first-line therapy for patients with intermediate HCC. However, we have to be careful about liver function. Liver function is known to [impact] overall survival in patients with HCC, so liver function may be an important factor to decide treatment procedure for the patient.

TARGETED ONCOLOGY: How could wider adoption of this therapy help improve outcomes in these patients?

The important thing is to perform lenvatinib therapy safely and effectively. During lenvatinib therapy, so many AEs could happen, and I think the outcome of lenvatinib therapy would not be as good. To spread our concept, we have to make it clear that the baseline function or stages of the patient [impact] how we can give lenvatinib therapy safely and effectively. That means to avoid the discontinuation [of treatment] due to AEs. This is 1 of the most important factors.

REFERENCE

Tsuchiya K, Kurosaki M, Kaneko S, et al. A nationwide multicenter study in patients with unresectable hepatocellular carcinoma treated with lenvatinib in real world practice in Japan. Presented at: 2020 ASCO Gastrointestinal Cancers Symposium; January 23-26, 2020; San Francisco, CA.

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