Perioperative, Adjuvant Nivolumab Versus Surgery With Surveillance: RFS in High-Risk RCC

Nivolumab is commonly used for the treatment of renal cell carcinoma (RCC) due to the efficacy seen in past trials, including CheckMate 025 and CheckMate 214.

Standard-of-care treatment for patients with intermediate- to high-risk RCC consists of partial or radical nephrectomy and surveillance, but a recent study by Mohamad E. Allaf, MD, and colleagues compared the use of nivolumab before nephrectomy followed by adjuvant nivolumab with surgery only in patients with high-risk RCC to determine which treatment offered better rates of recurrence-free survival (RFS).

The open-label, phase 3 PROSPER EA8143 trial enrolled 819 patients from the United States and Canada. Participants were 18 years of age or older, had an Eastern Cooperative Oncology Group performance status of 0-1, and had previously untreated clinical stage T2 or greater or T_any N+ RCC of clear cell or non-clear cell histology, with planned partial or radical nephrectomy. Patients with oligometastatic disease were also eligible for inclusion if found to be disease free at other disease sites within 12 weeks of surgery.

Patients were randomly assigned to receive nivolumab in combination with surgery (nivolumab group; n=404) or surgery only followed by surveillance (surgery group; n=415). Patients in the nivolumab group were administered nivolumab 480 mg before surgery, followed by 9 adjuvant doses.

The primary end point was investigator-reviewed RFS in patients with RCC regardless of histology. Safety was also assessed in all randomly assigned patients.

Between February 2017 and June 2021, treatment was started in 366 (91%) patients in the nivolumab group and 387 (93%) in the surgery group. Due to futility, the trial was stopped at a planned interim analysis in March 2022.

The median follow-up rates were 30.4 months (range, 21.5-42.4 months) in the nivolumab group and 30.1 months (range, 21.9-41.8 months) in the surgery group. A total of 381 (94%) patients in the nivolumab group and 399 (96%) in the surgery group were included in the RFS analysis.

As of the data cutoff in May 2023, RFS rates were not significantly different between the nivolumab (125 [33%] of 381 experienced RFS events) and surgery groups (133 [33%] of 399; hazard ratio, 0.94; 95% CI, 0.74-1.21; one-sided P=0.32).

Common grade 3-4 treatment-related adverse events (AEs) included elevated lipase, anemia, increased alanine aminotransferase, abdominal pain, and increased serum amylase. Grade 3-5 AEs of any cause, including anemia, hypertension, and elevated lipase, occurred in 177 (48%) patients in the nivolumab group and 93 (24%) in the surgery group. In the nivolumab and surgery groups, respectively, 48 (12%) and 40 (10%) patients died; 8 (2%) and 3 (1%) deaths, respectively, were determined to be treatment related.

The use of perioperative nivolumab before nephrectomy followed by adjuvant nivolumab was not found to improve RFS over surgery followed by surveillance in patients with high-risk RCC.