Can Molecular Classifications Help Tailor First-line Treatment of Metastatic Renal Cell Carcinoma? A Systematic Review of Available Models

Leibovich, 2010, Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma, J Urol, 183, 1309, 10.1016/j.juro.2009.12.035 Lipworth, 2016, Renal cell cancer histological subtype distribution differs by race and sex, BJU Int, 117, 260, 10.1111/bju.12950 SEER. Cancer of the kidney and renal pelvis—Cancer Stat Facts. https://seer.cancer.gov/statfacts/html/kidrp.html. Motzer, 2018, Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma, N Engl J Med, 378, 1277, 10.1056/NEJMoa1712126 Rini, 2019, Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma, N Engl J Med, 380, 1116, 10.1056/NEJMoa1816714 Albiges, 2019, Updated European Association of Urology guidelines on renal cell carcinoma: immune checkpoint inhibition is the new backbone in first-line treatment of metastatic clear-cell renal cell carcinoma, Eur Urol, 76, 151, 10.1016/j.eururo.2019.05.022 Escudier, 2019, Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up, Ann Oncol, 30, 706, 10.1093/annonc/mdz056 Motzer, 2019, NCCN guidelines insights: kidney cancer, version 2.2020, J Natl Compr Canc Netw, 17, 1278, 10.6004/jnccn.2019.0054 Bedke, 2021, Updated European Association of Urology guidelines on renal cell carcinoma: nivolumab plus cabozantinib joins immune checkpoint inhibition combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma, Eur Urol, 79, 339, 10.1016/j.eururo.2020.12.005 Heng, 2009, Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study, J Clin Oncol, 27, 5794, 10.1200/JCO.2008.21.4809 Casuscelli, 2017, Molecular classification of renal cell carcinoma and its implication in future clinical practice, Kidney Cancer, 1, 3, 10.3233/KCA-170008 Turajlic, 2018, Deterministic evolutionary trajectories influence primary tumor growth: TRACERx Renal, Cell, 173, 595, 10.1016/j.cell.2018.03.043 Page, 2021, The PRISMA 2020 statement: An updated guideline for reporting systematic reviews, J Clin Epidemiol., 134, 178, 10.1016/j.jclinepi.2021.03.001 Beuselinck, 2015, Molecular subtypes of clear cell renal cell carcinoma are associated with sunitinib response in the metastatic setting, Clin Cancer Res, 21, 1329, 10.1158/1078-0432.CCR-14-1128 McDermott, 2018, Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma, Nat Med, 24, 749, 10.1038/s41591-018-0053-3 Hakimi, 2019, Transcriptomic profiling of the tumor microenvironment reveals distinct subgroups of clear cell renal cell cancer: data from a randomized phase III trial, Cancer Discov, 9, 510, 10.1158/2159-8290.CD-18-0957 Motzer, 2020, Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial, Nat Med, 26, 1733, 10.1038/s41591-020-1044-8 Verbiest, 2018, Molecular subtypes of clear cell renal cell carcinoma are associated with outcome during pazopanib therapy in the metastatic setting, Clin Genitourin Cancer, 16, e605, 10.1016/j.clgc.2017.10.017 Motzer, 2013, Pazopanib versus sunitinib in metastatic renal-cell carcinoma, N Engl J Med, 369, 722, 10.1056/NEJMoa1303989 Motzer, 2019, Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma, N Engl J Med, 380, 1103, 10.1056/NEJMoa1816047 Choueiri, 2020, Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma, Ann Oncol, 31, 1030, 10.1016/j.annonc.2020.04.010 Tannir, 2021, Efficacy and safety of nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma, Clin Cancer Res, 27, 78, 10.1158/1078-0432.CCR-20-2063 Tucker, 2020, Predicting response to immunotherapy in metastatic renal cell carcinoma, Cancers, 12, 2662, 10.3390/cancers12092662 Vano, 2020, LBA25 Results from the phase II biomarker driven trial with nivolumab (N) and ipilimumab or VEGFR tyrosine kinase inhibitor (TKI) in naïve metastatic kidney cancer (m-ccRCC) patients (pts): the BIONIKK trial, Ann Oncol, 31, S1157, 10.1016/j.annonc.2020.08.2254 Hakimi, 2016, An integrated metabolic atlas of clear cell renal cell carcinoma, Cancer Cell, 29, 104, 10.1016/j.ccell.2015.12.004 Choueiri, 2018, Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial, Lancet Oncol, 19, 451, 10.1016/S1470-2045(18)30107-4 ClinicalTrials.gov. Avelumab in metastatic or locally advanced solid tumors (JAVELIN solid tumor) - full text view. https://clinicaltrials.gov/ct2/show/NCT01772004. Masiero, 2013, A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis, Cancer Cell, 24, 229, 10.1016/j.ccr.2013.06.004 Motzer, 2020, Biomarker analyses from the phase III CheckMate 214 trial of nivolumab plus ipilimumab (N+I) or sunitinib (S) in advanced renal cell carcinoma (aRCC), J Clin Oncol, 38, 5009, 10.1200/JCO.2020.38.15_suppl.5009 Becht, 2015, Prognostic and theranostic impact of molecular subtypes and immune classifications in renal cell cancer (RCC) and colorectal cancer (CRC), Oncoimmunology, 4, e1049804, 10.1080/2162402X.2015.1049804 Epaillard, 2020, BIONIKK: a phase 2 biomarker driven trial with nivolumab and ipilimumab or VEGFR tyrosine kinase inhibitor (TKI) in naïve metastatic kidney cancer, Bull Cancer, 107, eS22, 10.1016/S0007-4551(20)30283-6 Motzer, 2007, Sunitinib versus interferon alfa in metastatic renal-cell carcinoma, N Engl J Med, 356, 115, 10.1056/NEJMoa065044 Gerlinger, 2012, Intratumor heterogeneity and branched evolution revealed by multiregion sequencing, N Engl J Med, 366, 883, 10.1056/NEJMoa1113205 Marchioni, 2021, Biomarkers for renal cell carcinoma recurrence: state of the art, Curr Urol Rep, 22, 31, 10.1007/s11934-021-01050-0