(UroToday.com) The 2023 EAU annual meeting included a session on locally advanced kidney cancer, featuring a presentation by Dr. Furkan Dursun discussing the utility of adjuvant immunotherapy in high-risk non-metastatic renal cell carcinoma (RCC). Radical nephrectomy is the standard management for locoregional RCC, however, patients with adverse pathological features are at increased risk of recurrence ranging from 10% to 50%. IMmotion0101 and KEYNOTE 5642 trials investigated the adjuvant role of immune checkpoint inhibitors for high-risk clear cell RCC and have yielded conflicting results. Dr. Dursun and colleagues aimed to investigate real-world survival outcomes associated with the adjuvant use of immune checkpoint inhibitors in high-risk ccRCC using the National Cancer Database.
In this nationwide contemporary cohort study, patients with newly diagnosed non-metastatic high-risk clear cell RCC undergoing radical nephrectomy between 2015-2019 were included. High-risk RCC was defined as cT2 with Fuhrman grade 4 or cT3a with Fuhrman grade 3/4 or cT3b/T3c/T4 with any grade, or TxN+ any grade. Patients receiving adjuvant immune checkpoint inhibitors were classified as Group A and patients who did not receive adjuvant immune checkpoint inhibitors were classified as Group B. Inverse probability weighting (IPW)-adjusted Kaplan Meier curves were utilized to compare overall survival (OS) between the groups and cox proportional hazard models were utilized to identify the predictors for OS.
Overall, 768 patients met the inclusion criteria, including 270 patients in Group A and 498 patients in Group B. The mean age was 60.5 (SD 10.6) years, and 70.8% of patients were males. There 88.4% Caucasian pateints and 8.5% were Hispanics. The complete baseline characteristics are as follows:
The use of immune checkpoint inhibitors in the adjuvant setting for high-risk RCC increased from 17.4% (29 of 167) in 2015 to 61.8% (68 of 110) in 2019. The 5-year overall survival was 36.8% (95%CI, 25.9% -52.4%) for Group A while 50.1% (44.1%-56.4%) for Group B (p = 0.30). The 5-year OS remained similar between the two groups, even after IPW-adjusted cohort analysis (39.4% in Group A vs 47.9%, p = 0.17):
The use of adjuvant immune checkpoint inhibitors did not appear to be an independent predictor for OS on multivariable cox regression analysis (HR 1.14, p = 0.31). Several limitations of this study include: (i) it’s retrospective design, (ii) lack of control for confounding variables, (iii) lack of cancer specific survival and cause of death, and (iv) use of solely NCDB-based facilities.
Dr. Dursun concluded his presentation discussing the utility of adjuvant immune checkpoint inhibitors in high-risk non-metastatic renal cell carcinoma with the following take-home messages:
- The use of adjuvant immune checkpoint inhibitors in non-metastatic RCC with a high risk of relapse has increased substantially over the past years
- However, compared to adjuvant targeted therapy, adjuvant immune checkpoint inhibitors were not associated with an OS benefit
- Further studies to identify candidates for benefit with adjuvant immune checkpoint inhibitors are needed
Presented by: Furkan Dursun, MD, University of Texas Health, San Antonio, Dept. of Urology, San Antonio, Texas
Co-Authors: Garg H.1, Bhandari M.2, Noel O.V.1, Liss M.A.1, Kaushik D.1, Ramamurthy C.3, Mansour A.M.1
Affiliations: 1University of Texas Health, San Antonio, Dept. of Urology, San Antonio, United States of America, 2University of Texas Health, San Antonio, Dept. of Population Health Science, San Antonio, United States of America, 3University of Texas Health, Dept. of Medical Oncology, San Antonio, United States of America
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 European Association of Urology (EAU) 38th annual congress held in Milan, Italy between March 10-13, 2023
References:
- Pal SK, Uzzo R, Karam JA, et al. Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): A multicentre, randomized, double-blind, phase 3 trial. Lancet 10 Sept 2022 [Epub ahead of print].
- Choueiri TK, Tomczak P, Park SH, et al. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021 Aug 19;385(8):683-694.