Dr Grünwald on Examining Progression Patterns for Lenvatinib Plus Pembrolizumab in Advanced RCC

Viktor Grünwald, MD, PhD, professor, Interdisciplinary Genitourinary Oncology, the University Hospital Essen, discusses background for the investigation of first-line lenvatinib (Lenvima) plus pembrolizumab (Keytruda) in advanced renal cell carcinoma (RCC)and the rationale for examining patterns of progression and subsequent therapy for patients treated with the combination during the phase 3 CLEAR trial (NCT02811861).

In the primary analysis of the CLEAR trial, lenvatinib plus pembrolizumab significantly improved efficacy for patients with advanced RCC compared with sunitinib (Sutent), Grünwald begins. This finding was further confirmed in the final prespecified overall survival analysis of the trial. Subsequent analyses were conducted by Grunwald and colleagues to identify which patient subgroups benefitted most from lenvatinib plus pembrolizumab and to understand the clinical patterns that could guide the selection of this regimen in clinical practice.

The first aspect of these analyses explored individual progression patterns, Grünwald details. By expanding on the type of tumor shrinkage occurring in organs such as the liver, lymph nodes, or bone, this could better inform and personalize assessment of potential patient benefit with the doublet approach, Grünwald explains. To examine responses across tumors in different organs, time to progression was defined for each organ independently using lesions within each specific organ. Results presented at the 2024 ASCO Annual Meeting indicated a trend toward later progression in various organs for patients receiving the combination therapy. Additionally, hazard ratios for time to disease progression favored the lenvatinib plus pembrolizumab combination over sunitinib across different organs.

The second part of the analysis investigated whether tumor burden at the start of therapy influences outcomes from lenvatinib plus pembrolizumab, Grünwald continues. Although a strong association was not observed, a higher tumor burden was found to correlate with poor-risk features, he notes. However, the time of overall disease progression, the tumor burden of target lesions was lower in patients treated with lenvatinib plus pembrolizumab vs those treated with sunitinib, Grünwald states. Overall, these results reinforce the use of lenvatinib plus pembrolizumab as a first-line standard of care for advanced RCC, demonstrating its efficacy across different organs and regardless of initial tumor burden.