Frontline Combination Strategies in Patients With Clear-Cell RCC
Expert discussion focused on approved therapies for first-line kidney cancer treatment including combination therapies, immunotherapy, and tyrosine kinase inhibitors (TKIs) in various clinical scenarios.
Summary:
In the realm of first-line treatment for kidney cancer, several combination therapies have emerged as FDA-approved options based on compelling evidence from randomized trials. Notably, combinations involving VEGF receptor tyrosine kinase inhibitors (TKIs) and/or immunotherapy have shown superiority in both progression-free survival (PFS) and overall survival (OS) when compared to the use of sunitinib alone.
The lenvatinib and pembrolizumab combination, validated by the CLEAR trial, demonstrated benefits in both PFS and OS. Similarly, the axitinib and pembrolizumab combination, assessed in KEYNOTE-426, exhibited favorable outcomes in both PFS and OS. Another notable combination, cabozantinib and nivolumab, as studied in the CheckMate 9ER trial, showcased benefits in both OS and PFS. Additionally, the combination of ipilimumab plus nivolumab, investigated in the CheckMate 214 trial, received FDA approval specifically for intermediate- and poor-risk patients in the first-line kidney cancer setting.
While other combinations, like axitinib and avelumab, are FDA-approved, their use is less common due to the absence of a clear overall survival benefit in the Javelin Renal 101 trial. For patients unable to safely undergo immunotherapy, single-agent TKIs such as cabozantinib remain a viable option. The choice between immunotherapy combinations, immunotherapy and TKI combinations, or single-agent TKIs depends on patient fitness and eligibility. Studies such as CLEAR, KEYNOTE-426, and CheckMate 9ER emphasized the superiority of combination therapies over single-agent TKIs in terms of OS, PFS, and overall response rate. The decision of which combination to use is influenced by the patient’s tolerability and specific characteristics, such as the half-life of the TKI and potential dose-limiting toxicities.
In the assessment of the selection between combination therapies, the consideration of patient-specific factors is crucial. For instance, patients with concerns about toleration may find the combination with axitinib preferable due to its short half-life and lower incidence of dose-limiting toxicities. Conversely, single-agent treatment may be appropriate for individuals with contraindications or comorbidities that limit their eligibility for combination therapies, such as uncontrolled autoimmune conditions or a history of solid organ transplantation. Overall, the evolving landscape of first-line kidney cancer treatment emphasizes the importance of tailoring therapeutic approaches based on individual patient characteristics and risk factors.
Summary is AI-generated and reviewed by Cancer Network editorial staff.
