(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a kidney and bladder cancers poster session. Dr. Naomi Haas presented the results of a post-hoc analysis from PROSPER (ECOG-ACRIN EA8143), which evaluated perioperative nivolumab versus observation in renal cell carcinoma (RCC) patients undergoing a radical or partial nephrectomy.
PROSPER was a phase 3, open-label trial that examined the effect of priming the immune system with neoadjuvant nivolumab prior to nephrectomy, followed by adjuvant nivolumab in patients with high-risk RCC compared to surgery alone. PROSPER included patients with clinical stage ≥T2 or TanyN+ RCC planned for nephrectomy (partial or radical). In the investigational arm, nivolumab was administered (480mg IV q4 weeks) with 1 dose prior to surgery followed by 9 adjuvant doses. The control arm was surgery followed by surveillance without a placebo. The trial schema for PROSPER is as follows:
PROSPER failed to meet its primary endpoint with recurrence-free survival not significantly improved with addition of perioperative nivolumab (HR: 0.97, 95% CI: 0.74 – 1.28, 1-sided p-value=0.43).
During the conduct of the PROSPER trial, the study protocol was amended to require a core renal biopsy only in patients randomized to the nivolumab arm (initially in all patients), in an effort to address concerns that a kidney core biopsy might not provide an accurate diagnosis and may delay surgery due to adverse events or scheduling logistics. In this post-hoc analysis of the PROSPER trial, the authors report the accuracy and safety of primary tumor core biopsies in predicting final histology and nuclear grade by both site and central pathology review, as well as time from enrollment to surgery.
The authors reported concordance of both core biopsy and primary tumor by site and central pathology review of histology and grade (1-2 versus 3-4), as well as the corresponding Cohen’s Kappa value, which quantifies the concordance between readers. Adverse events relating to core biopsies and preoperative nivolumab, as well as the time from enrollment to surgery for each arm, comparing pre- and post-amendment outcomes, were also reported.
Core biopsies were performed in 387/404 and 171/415 patients in the nivolumab +surgery and surgery only arms, respectively. 632 patients had both central pathology and site review available. Of the 819 randomized patients, 41 (5%) did not have an RCC, 26 (63%) of which were identified via the core biopsy. The median times from enrollment to surgery for the nivolumab and control arms pre-amendment were 32 versus 19 days, and post-amendment were 21 versus 14 days, respectively. The median number of days from last preoperative nivolumab to surgery was 14 days (IQR: 9 -20).
Adverse events related to core biopsies, generally from bleeding, were reported in 13/558 (2.3%) patients, with 2/13 biopsies resulting in life-threatening complications. Among patients receiving nivolumab, 6% had grade 3 or worse adverse events attributed to nivolumab pre-operatively. Overall, 51% of patients had any grade adverse event attributed to nivolumab.
The concordance between biopsies and primary tumor pathologies for determining histological subtype was Kappa = 0.62. The agreement between central pathology and originating site review of primary tumor for determining nuclear grade was Kappa = 0.56, and concordance of histology was Kappa = 0.78.
Dr. Haas concluded that the use of core biopsies in the PROSPER trial in advance of neoadjuvant therapy was generally safe, largely consistent with primary tumor histology and grade, and did not delay resection of the primary tumor. Adverse events of preoperative nivolumab were consistent with nivolumab adverse events in metastatic disease. Overall, it appears that this approach is valid for future neoadjuvant trials.
Presented by: Naomi B. Haas, MD, Professor, Director of the Prostate and Kidney Cancer Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.