Reviewing Adjuvant Therapies for Localized RCC

By Emily Menendez - November 17, 2022

The use of immune checkpoint inhibitors for the treatment of localized renal cell carcinoma (RCC) has evolved over the past several years, with drugs such as nivolumab and pembrolizumab becoming approved for treatment use. Localized RCC can be cured through surgery, but many patients may need additional treatment in the form of immune checkpoint inhibitors as adjuvant therapy. A recent study looks at previous adjuvant therapy treatments to determine the future of adjuvant therapy use for localized RCC.

IFNα and IL-2

High-dose bolus interleukin-2 (IL-2) used postoperatively in high-risk RCC patients was examined in a 2000 study by Clark et al., but it was shut down early, as it showed similar rates of disease-free survival (DFS) for both the IL-2 and placebo groups.

Another study carried out by the Eastern Cooperative Oncology Group/Intergroup Trial examined the effect of adjuvant interferon alfa (IFNα) in 283 patients after receiving total resection of locally extensive RCC. Researchers compared observation to IFNα in 283 patients after a full resection of locally extensive RCC and found that the median overall survival rate was 7.4 years in the observation arm and 5.1 years in the treatment arm.

A treatment of low-dose IL-2 combined with IFN was researched in the POLAR-01 study, which involved 310 patients with fully resected pT2–3b pN0–3 M0 tumors. Results of the study showed similar rates of relapse-free survival and overall survival, with an estimated hazard ratio of 0.84 and 1.07.

VEGFR Tyrosine Kinase Inhibitors

VEGFRs have been the standard of care for treating metastatic RCC, and have been explored in the adjuvant setting in several randomized controlled trials.

The ASSURE study examined the use of the VEGFR treatments sunitinib and sorafenib in 1943 patients across 54 weeks, in which patients were given 50 mg of sunitinib daily for the first 4 weeks of each 6- week cycle, and then given 400 mg of sorafenib twice per day throughout each cycle, or placebo. No significant difference was seen in disease-free survival (DFS), however, and overall survival (OS) did not differ between the two trial groups. Sunitinib had a 5-year OS rate of 77.9%, while sorafenib had an 80.5% OS rate, and placebo had an 80.3% rate.

The S-TRAC trial also investigated the effects of adjuvant sunitinib in 615 patients with non-metastatic locoregional RCC. The median DFS rate for sunitinib was 6.8 years and 5.6 years in the placebo group, and the results led the US Food and Drug Administration to expand sunitinib’s indication to include the treatment of patients at high risk for recurrence after nephrectomy.

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors, including pembrolizumab and nivolumab, have been approved for the adjuvant treatment of urothelial carcinoma patients with high risk of recurrence after radical resection. The Keynote-564 study examined the effect of pembrolizumab as an adjuvant therapy by treating patients with 200 mg of pembrolizumab intravenously every 3 weeks, or placebo for up to 1 year. Results from the study showed that the risk of recurrence or death was 32% lower in the pembrolizumab arm when compared to the placebo arm.

Many adjuvant treatments for RCC and localized RCC have shown promising results, while many other trials are still ongoing to research further treatments, such as Checkmate 914 and the RAMPART study.

 

Reference

Adjuvant Therapy for Renal Cell Carcinoma, Finally a New Standard?

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