Four-Year Follow-Up Confirms Lenvatinib/Pembrolizumab Safety in RCC

In an interview with CancerNetwork^®, Thomas E. Hutson, DO, PharmD, FACP, spoke about how the safety profile of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) in patients with advanced clear cell renal cell carcinoma (RCC) was maintained after 4 years of follow-up in the phase 3 CLEAR study (NCT0281186).¹

Hutson, director of the Urologic Oncology Program and co-chair of the Urologic Cancer Research and Treatment Center at Baylor University Medical Center in Dallas, as well as a professor of Medicine at Texas A&M College of Medicine, said that any adverse effects (AEs) in the trial were manageable with dose interruptions, reductions, or modifications in combination with best supportive care. Additionally, the 4-year follow-up safety data were consistent with reports from the initial preliminary analysis of the CLEAR study that led to the regimen’s regulatory approval.

The FDA approved lenvatinib plus pembrolizumab for this patient population in August 2021.²

According to data presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, the most common any-grade treatment-related AEs in the lenvatinib plus pembrolizumab and sunitinib (Sutent) arms, respectively, included diarrhea (56.0% vs 46.3%), hypertension (54.3% vs 40.3%), hypothyroidism (44.9% vs 24.1%), and decreased appetite (35.5% vs 26.3%).

Transcript:

The safety—as reported in the initial preliminary analysis of the data that resulted in [lenvatinib plus pembrolizumab's] regulatory approval—is maintained, confirming that there are no new additional safety signals with longer follow-up. The diarrhea, hypertension, and fatigue, which are the most commonly reported [adverse] effects, are there throughout the therapy with no additional worsening in the way that the [adverse] effects are managed, as is indicated in the product labeling, through dose interruption, dose reduction, and then best supportive care.

This continues to be the strategy we want to employ in managing the [adverse] effects and keeping the dose intensity where it needs to be so that patients get this long-term benefit from therapy.

References

1. Motzer RJ, Porta C, Eto M, et al. Final prespecified overall survival (OS) analysis of CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab (L+P) vs sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). J Clin Oncol. 2023;41(suppl 16):4502. doi:10.1200/JCO.2023.41.16_suppl.4502
2. FDA approves Keytruda (pembrolizumab) plus Lenvima (lenvatinib) combination for first-line treatment of adult patients with advanced renal cell carcinoma (RCC). News release. Merck. August 11, 2021. Accessed July 19, 2023. https://bwnews.pr/3m0p3Vh