We determined the oncologic outcomes and safety profiles of adjuvant immune checkpoint inhibitors (ICIs) compared to adjuvant tyrosine kinase inhibitors (TKIs) in patients at high risk after nephrectomy for clinically nonmetastatic renal cell carcinoma (RCC). Network meta-analyses were conducted for disease-free survival (DFS), overall survival (OS), and adverse events (AEs) with placebo as the common comparator arm. Six trials (KEYNOTE-564, S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our analysis. Compared to placebo, both pembrolizumab (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.51-0.92) and pazopanib 800 mg (HR 0.69, 95% CI 0.49-0.97) were significantly associated with better DFS. Adjuvant pembrolizumab (HR 0.54, 95% CI 0.30-0.97) was significantly associated with better OS compared to TKIs (HR 0.93, 95% CI 0.83-1.04). Analysis of treatment ranking revealed that pembrolizumab was the best treatment with regard to both DFS and OS and had the lowest likelihood of any-grade and high-grade AEs in comparison to TKIs. The superior oncologic benefit of pembrolizumab and its better toxicity profile support it as the new standard of care in the adjuvant setting for nephrectomy patients at high risk of RCC relapse. PATIENT SUMMARY: For patients with kidney cancer at high risk of relapse after surgical removal of their kidney, postoperative therapy with the immune checkpoint inhibitor pembrolizumab offers the best risk/benefit ratio.
European urology oncology. 2022 Jan 03 [Epub ahead of print]
Ekaterina Laukhtina, Fahad Quhal, Keiichiro Mori, Reza Sari Motlagh, Pawel Rajwa, Takafumi Yanagisawa, Hadi Mostafaei, Frederik König, Abdulmajeed Aydh, Benjamin Pradere, Dmitry Enikeev, Pierre I Karakiewicz, Manuela Schmidinger, Shahrokh F Shariat
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Silesia, Zabrze, Poland., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Faisal Medical City, Abha, Saudi Arabia., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Canada., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan. Electronic address: .