Dr Basu on the Potential Utility of MRD-Guided Adjuvant Therapy in RCC

Arnab Basu, MD, MPH, FACP, assistant professor, genitourinary medical oncology, the University of Alabama in Birmingham Medicine, discusses the rationale for evaluating the use of molecular residual disease (MRD)–guided adjuvant therapy in the ongoing phase 2 MRD Gate RCC clinical trial (NCT06005818) in patients with renal cell carcinoma (RCC).

Despite ongoing efforts to enhance outcomes for patients with high-risk resected RCC, recurrence rates can vary from 40% to 50% in this patient population, Basu begins. The primary focus has been on improving overall survival (OS) and progression-free survival (PFS) with the use of adjuvant approaches; however, many adjuvant trials in RCC have not yielded promising results, Basu states.

Among the trials that have garnered positive results for these patients is the phase 3 S-TRAC trial (NCT00375674) evaluating sunitinib (Sutent) in patients with clear-cell RCC at high risk for tumor recurrence following nephrectomy, Basu reports. The trial demonstrated a benefit in disease-free survival with the agent, but a significantly higher rate of toxicities compared with treatment of placebo, he details. More recently, the phase 3 KEYNOTE-564 trial (NCT03142334) has shown improvement in both PFS and OS with adjuvant pembrolizumab (Keytruda) vs placebo, albeit with a moderate magnitude of benefit, Basu states.

It is still unclear why these trials were successful when so many others failed to meet their primary end point, Basu says. One potential explanation is the conventional approach of treating all patients with adjuvant therapy without considering individual disease characteristics or optimal treatment regimens, Basu posits.

To address this issue, research has shifted towards identifying patients with minimal residual disease (MRD) who may benefit most from adjuvant therapy, Basu continues. The MRD gate RCC study was designed to refine the risk-benefit balance by selecting patients based on MRD status, he elucidates. This could provide insight into the outcomes of patients with MRD-positive RCC, potentially offering a more tailored and effective approach to adjuvant treatment, Basu explains.

With further research and funding, the study aims to extend its analysis to encompass longer-term outcomes beyond the initial 1-year assessment, Basu notes. Ultimately, the goal of MRD gate RCC is to optimize treatment strategies and improve outcomes for patients with high-risk resected RCC, Basu emphasizes. The study is currently recruiting patients, with an estimated completion date of June 30, 2025.