Introduction:

The emergence of immune checkpoint inhibitors as effective therapy for patients with metastatic renal cell carcinoma (RCC) has prompted significant interest in this class in both the neo-adjuvant and adjuvant settings. The changes that result from immune checkpoint inhibition in the renal and perinephric tissue remains poorly described. The surgical safety and efficacy for partial and radical therapy for patients with complex locally advanced renal tumors is not well established. We s evaluated surgical outcomes for patients after neoadjuvant immune checkpoint inhibitor therapy.

Methods:

A phase 1b trial of neoadjuvant durvalumab (anti-PDL1) +/- tremelimumab (anti-CTLA-4) in locally advanced renal cell carcinoma was performed at two sites (Cleveland Clinic Foundation and University of Minnesota) between 2016 and 2020 (NCT02762006). Inclusion criteria included RCC clinical stage T2b-4 and/or N1, M0 disease, ECOG 0-1, and adequate organ function. A total of four cohorts were evaluated. In the neoadjuvant setting, cohort 1 received durvalumab (D) x 1, and cohorts 2, 2a, and 3 received D + Tremelimumab (T) x 1 dose. In the adjuvant setting, Cohorts 1-2 received one dose of D, cohort 2a received D for one year, and cohort 3 received D+T x 1 then D for a full year. Pre- and post-surgical patient characteristics were evaluated, and descriptive statistics are presented.

Results:

Twenty-five patients (pts) were analyzed and 23 underwent both neoadjuvant and adjuvant therapy (Table 1; 2 pts received neo-adjuvant alone). Tumors were surgically complex with the most common RENAL score being 11xh. Renal vein involvement was present in 6 tumors (Level 1 (2 pts), Level 2 (1 pt), Level 3 (2 pts), Level 4 (1 pt)). Tumors were managed with minimally-invasive (n=8) or open (n=17) approaches and the majority of patients underwent radical nephrectomy (n=23). Median estimated blood loss was 375cc (IQR:188–775). Three patients were transfused postoperatively for a total of 4 units. No intraoperative complications were noted. Margins were positive for 5 patients all located at the renal vein wall. Median length of stay was 4 days (IQR:3–5). Three patients required readmission for diabetic ketoacidosis, thrombocytopenia, and pulmonary embolism.  There were five 30-day and 90-day Clavien complications (Table 2). 

Conclusion:

Surgery for locally advanced renal cell carcinoma is safe for patients after neoadjuvant durvalumab +/- tremelimumab. 

Funding: AstraZeneca