Dr Hahn on the Phase 2 LenCabo Trial in RCC

In an interview with Targeted Oncology, Andrew Hahn, MD, medical oncologist at MD Anderson Cancer Center, details the findings of a phase 2, randomized trial (LenCabo) presented at the European Society for Medical Oncology (ESMO) Congress 2025, which compared the efficacy and safety of lenvatinib (Lenvima) plus everolimus versus single-agent cabozantinib (Cabometyx) in patients with metastatic clear cell renal cell carcinoma (ccRCC) who had progressed following treatment with a PD-1 checkpoint inhibitor.

The study's primary end point, progression-free survival (PFS), was significantly improved by the combination therapy. Patients receiving lenvatinib/everolimus achieved a median PFS of 15.7 months compared with 10.2 months for those on cabozantinib. This result demonstrated a 49% reduction in the risk of disease progression or death for the combination group (HR, 0.51; P =.02).

The combination also yielded a numerically higher objective response rate (ORR) at 52.6% vs 38.6% for cabozantinib, though this difference did not meet the bar for statistical significance. Overall survival data remained immature at the time of the analysis.

While more effective, the combination was associated with greater toxicity. The incidence of grade 3 or 4 adverse events (AEs) was higher in the lenvatinib/everolimus arm at 67.5% compared with 50% for cabozantinib. Treatment discontinuation due to AEs also occurred in 20% of the combination group versus 10.9% of the single-agent group.

In conclusion, the trial established lenvatinib plus everolimus as a superior second-line or later option in terms of PFS and response, representing the first head-to-head comparison in this post–PD-1 setting. However, clinicians must weigh the significant efficacy benefit against the higher rate of toxicity when determining the best treatment sequence for individual patients.