Pembrolizumab plus lenvatinib for radically unresectable or metastatic renal cell carcinoma in the Japanese population

ABSTRACT

Introduction

At present, the combination of immune checkpoint inhibitors (ICIs) or an ICI and a tyrosine kinase inhibitor (TKI) are the main treatment options as first-line therapy for metastatic renal cell cancer (mRCC). Among them, pembrolizumab plus lenvatinib was recently launched in Japanese clinical practice.

Area covered

In this review, the efficacies and safety profiles of pembrolizumab plus lenvatinib for mRCC between Japanese and global populations are compared. In addition, lenvatinib is currently available for the treatment of not only mRCC but also of endometrial, thyroid, thymic, and hepatocellular cancers. We briefly summarized the characteristics of pembrolizumab plus lenvatinib or lenvatinib monotherapy for these malignancies. Finally, the characteristics of pembrolizumab plus lenvatinib for mRCC in the Japanese population are briefly elucidated.

Expert opinion

In order to develop optimal personalized treatment for mRCC patients, it is necessary for physicians who treat mRCC patients to possess in-depth knowledge of not only the efficacy and safety profile of the respective therapies but also of the interpatient heterogeneities between Japanese and global populations.

KEYWORDS:

• Immune checkpoint inhibitor (ICI)
• tyrosine kinase inhibitor (TKI)
• combination therapy
• pembrolizumab plus lenvatinib
• metastatic renal cell cancer (mRCC)
• interpatient heterogeneity

Article highlights

• At present, combinations of ICIs or TKI/ICI are the standard treatment options as first-line therapy for mRCC.

• Among the combination therapies, pembrolizumab plus lenvatinib just launched in 2022 Japanese clinical practice.

• We compare the efficacy and safety profile of pembrolizumab plus lenvatinib between Japanese and global populations.

• Efficacies, which include progression-free survival (PFS) and overall survival (OS) periods, complete response (CR) rates, objective response rates (ORRs), and disease control rates (DCRs), are comparable between these populations. The long PFS period (22.1 months), high CR rates (19.0%), high ORR (69.0%), and high DCR (95.2%) are attractive in the Japanese population.

• The incidences of specific adverse events, which include palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hypothyroidism, and hypertension, appear to be higher in Japanese patients than in the overall population.

• As a result of the treatment-related dose reduction for these adverse events, the relative dose intensities (RDIs) of lenvatinib appear to be lower in Japanese patients than in the overall population.

• Nonetheless, due to the significance of the initial RDI of lenvatinib, its starting dose of 20 mg should not be reduced.

Declaration of interest

T Yuasa received remuneration for a lecture from Eizai (Tokyo, Japan) and MSD Japan (Tokyo, Japan).

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737140.2023.2200170.

Additional information

Funding

This work was partly supported by JSPS KAKENHI Grant Number 21K09342 (S.K).