@article{d0593757adbc4246883bb1bc97202b88,
title = "A Plea for Optimizing Selection in Current Adjuvant Immunotherapy Trials for High-risk Nonmetastatic Renal Cell Carcinoma According to Expected Cancer-specific Mortality: Clinical Genitourinary Cancer",
abstract = "Background: Tyrosine kinase inhibitor-based adjuvant therapy showed no survival benefits for patients with high-risk nonmetastatic renal cell carcinoma (nmRCC). Five randomized immune-oncology checkpoint inhibitor trials are ongoing. We assessed the effect of stage, grade, and histologic type on cancer-specific mortality (CSM) in candidates for 1 of the 4 North American ongoing immune-oncology checkpoint inhibitor trials of high-risk nmRCC. Patients and Methods: From the Surveillance, Epidemiology, and End Results database (2001-2015), we identified patients who had undergone surgery for nmRCC and had met the inclusion criteria for the PROSPER RCC (nivolumab in treating patients with localized kidney cancer undergoing nephrectomy), CheckMate 914 (a study comparing the combination of nivolumab and ipilimumab versus placebo in participants with localized renal cell carcinoma), KEYNOTE-564 [safety and efficacy study of pembrolizumab (MK-3475) as monotherapy in the adjuvant treatment of renal cell carcinoma post nephrectomy], or IMmotion010 [a study of atezolizumab as adjuvant therapy in participants with renal cell carcinoma (RCC) at high risk of developing metastasis following nephrectomy] trials. Kaplan-Meier and multivariable Cox regression models were used to assess the 10-year CSM rates in the overall cohort according to stage, grade, and histologic characteristics, and in 4 generated random samples according to the eligible patients for each of the 4 trials. Results: Of 116,750 patients who had undergone surgery for nmRCC, 18,559 (15.9%) had fulfilled the inclusion criteria for 1 of the 4 trials. The greatest proportion of higher stage and grade combinations and sarcomatoid histologic features would have qualified for IMmotion010, followed by KEYNOTE-564, CheckMate 914, and PROSPER RCC. Multivariable Cox regression models demonstrated the most unfavorable prognosis for stage N1 grade 3/4 (hazard ratio [HR], 11.5; P ",
keywords = "Adjuvant therapy, Clear cell, Immune checkpoint inhibitors, Nephrectomy, Sarcomatoid, atezolizumab, ipilimumab, nivolumab, pembrolizumab, placebo, adult, aged, Article, cancer adjuvant therapy, cancer grading, cancer immunotherapy, cancer mortality, cancer patient, cancer risk, cancer specific survival, cancer staging, cancer surgery, cohort analysis, female, histopathology, human, kidney cancer, major clinical study, male, metastasis, monotherapy, partial nephrectomy, radical nephrectomy, randomized controlled trial (topic), renal cell carcinoma",
author = "C. Palumbo and E. Mazzone and F.A. Mistretta and S. Knipper and P. Perrotte and S.F. Shariat and F. Saad and A. Kapoor and J.-B. Lattouf and C. Simeone and A. Briganti and A. Antonelli and P.I. Karakiewicz",
note = "Cited By :2 Export Date: 4 March 2021 Correspondence Address: Palumbo, C.; Department of Urology, Piazzale Spedali Civili 1, Italy; email: palumbo.carlotta@gmail.com Chemicals/CAS: atezolizumab, 1380723-44-3; ipilimumab, 477202-00-9; nivolumab, 946414-94-4; pembrolizumab, 1374853-91-4 Tradenames: mk 3475 References: Ravaud, A., Motzer, R.J., Pandha, H.S., Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy (2016) N Engl J Med, 375, pp. 2246-2254; Haas, N.B., Manola, J., Uzzo, R.G., Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial (2016) Lancet, 387, pp. 2008-2016; Motzer, R.J., Haas, N.B., Donskov, F., Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma (2017) J Clin Oncol, 35, pp. 3916-3923; Gross-Goupil, M., Kwon, T.G., Eto, M., Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial (2018) Ann Oncol, 29, pp. 2371-2378; Meissner, M.A., McCormick, B.Z., Karam, J.A., Wood, C.G., Adjuvant therapy for advanced renal cell carcinoma (2018) Exp Rev Anticancer Ther, 18, pp. 663-671; Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy https://clinicaltrials.gov/ct2/show/NCT03055013, Available at: (Accessed 11 January 2019); A Study Comparing the Combination of Nivolumab and Ipilimumab Versus Placebo in Participants With Localized Renal Cell Carcinoma https://clinicaltrials.gov/ct2/show/NCT03138512, Available at: (Accessed 11 January 2019); Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564) https://clinicaltrials.gov/ct2/show/NCT03142334, Available at: (Accessed 11 January 2019); A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy https://clinicaltrials.gov/ct2/show/NCT03024996, Available at: (Accessed 11 January 2019); Renal Adjuvant Multiple Arm Randomised Trial https://clinicaltrials.gov/ct2/show/NCT03288532, Available at: (Accessed 11 March 2019); Bandini, M., Smith, A., Zaffuto, E., Effect of pathological high-risk features on cancer-specific mortality in non-metastatic clear cell renal cell carcinoma: a tool for optimizing patient selection for adjuvant therapy (2018) World J Urol, 36, pp. 51-57; Sun, M., Marconi, L., Eisen, T., Adjuvant vascular endothelial growth factor–targeted therapy in renal cell carcinoma: a systematic review and pooled analysis (2018) Eur Urol, 74, pp. 611-620; Ljungberg, B., Albiges, L., Abu-Ghanem, Y., European Association of urology guidelines on renal cell carcinoma: the 2019 update (2019) Eur Urol, 75, pp. 799-810; Karakiewicz, P.I., Zaffuto, E., Kapoor, A., Kidney Cancer Research Network of Canada (KCRNC) consensus statement on the role of adjuvant therapy after nephrectomy for high-risk, non-metastatic renal cell carcinoma: a comprehensive analysis of the literature and meta-analysis of randomized controlled trials (2018) Can Urol Assoc J, 12, pp. 173-180; McDermott, D.F., Huseni, M.A., Atkins, M.B., Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma (2018) Nat Med, 24, pp. 749-757; Motzer, R.J., Escudier, B., McDermott, D.F., Nivolumab versus everolimus in advanced renal-cell carcinoma (2015) N Engl J Med, 373, pp. 1803-1813; Motzer, R.J., Tannir, N.M., McDermott, D.F., Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma (2018) N Engl J Med, 378, pp. 1277-1290; Bellmunt, J., de Wit, R., Vaughn, D.J., Pembrolizumab as second-line therapy for advanced urothelial carcinoma (2017) N Engl J Med, 376, pp. 1015-1026",
year = "2020",
doi = "10.1016/j.clgc.2019.11.010",
language = "English",
volume = "18",
pages = "314",
journal = "Clin. Genitourin. Cancer",
issn = "1558-7673",
publisher = "Elsevier Inc.",
number = "4",
}