Adjuvant Therapy in High-Risk Renal Cell Carcinoma

There currently is not a designated standard adjuvant therapy for patients with renal cell carcinoma (RCC) at high risk of recurrence following resected, says Thomas E. Hutson, DO, PharmD. Recent studies have reported no benefit in disease-free survival (DFS) in locally advanced RCC from adjuvant therapy with the VEGF TKIs sunitinib or sorafenib.

In the phase III ASSURE trial, the median DFS was 5.6 years in both the sorafenib and sunitinib arms and 5.7 years in the placebo arm. These anti-angiogenic agents function in the tumor microenvironment level and are not directly cytotoxic to a micrometastatic cell, notes Hutson.

Researchers are still exploring whether TKIs have a role in the adjuvant setting for patients with RCC. Clinical trial protocols have allowed for the initiation of therapies at a lower dose, gradually escalating up to full dose to improve tolerance. Dose-reduction strategies may compromise the efficacy of the drug, says Hutson.

Checkpoint inhibitors have a favorable tolerability profile, where patients can stay on these therapies for long periods of time in the adjuvant setting. Although PD-1 inhibitors are associated with adverse events, says David F. McDermott, MD, these effects do not accumulate over time.

Patients at high risk of recurrence need to participate in clinical trials, states McDermott. A better biomarker may be needed before launching these trials, allowing clinicians to select patients who are more likely to benefit, comments McDermott. Other treatments under investigation in this setting include everolimus and dendritic cell vaccines.