Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial
Open accessAbstract
We report on molecular analyses of baseline tumor samples from the phase 3 JAVELIN Renal 101 trial (n = 886; NCT02684006 ), which demonstrated significantly prolonged progression-free survival (PFS) with first-line avelumab + axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We found that neither expression of the commonly assessed biomarker programmed cell death ligand 1 (PD-L1) nor tumor mutational burden differentiated PFS in either study arm. Similarly, the presence of FcɣR single nucleotide polymorphisms was unimpactful. We identified important biological features associated with differential PFS between the treatment arms, including new immunomodulatory and angiogenesis gene expression signatures (GESs), previously undescribed mutational profiles and their corresponding GESs, and several HLA types. These findings provide insight into the determinants of response to combined PD-1/PD-L1 and angiogenic pathway inhibition and may aid in the development of strategies for improved patient care in aRCC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Avelumab plus axitinib was approved by the FDA as the initial-line treatment for RCC, based on JAVELIN Renal 101.
“Besides pembrolizumab plus axitinib, nivolumab plus cabozantinib (based on CheckMate-9ER) [112] and avelumab plus axitinib (based on JAVELIN Renal 101) [113] were also approved by the FDA as the initial-line treatment for RCC.”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [113]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
WGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252 · see citing works
Regularization and Variable Selection Via the Elastic Net
Zou, H., & Hastie, T. (2005) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.1467-9868.2005.00503.x · Cited by 20,957 · see citing works
The Molecular Signatures Database Hallmark Gene Set Collection
Liberzon, A., Birger, C., Thorvaldsdóttir, H., Ghandi, M., Mesirov, J. P., & Tamayo, P. (2015) · Cell Systems · doi:10.1016/j.cels.2015.12.004 · Cited by 13,807 · see citing works
Robust enumeration of cell subsets from tissue expression profiles
Newman, A. M., Liu, C. L., Green, M. R., Gentles, A. J., Feng, W., Xu, Y., Hoang, C. D., Diehn, M., & Alizadeh, A. A. (2015) · Nature Methods · doi:10.1038/nmeth.3337 · Cited by 12,116 · see citing works
Modeling Survival Data: Extending the Cox Model
Therneau, T. M., & Grambsch, P. M. (2000) · Statistics for Biology and Health · doi:10.1007/978-1-4757-3294-8 · Cited by 8,674 · see citing works
Molecular signatures database (MSigDB) 3.0
Liberzon, A., Subramanian, A., Pinchback, R., Thorvaldsdóttir, H., Tamayo, P., & Mesirov, J. P. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr260 · Cited by 7,111 · see citing works
Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma
Motzer, R. J., Tannir, N. M., McDermott, D. F., Arén Frontera, O., Melichar, B., Choueiri, T. K., Plimack, E. R., Barthélémy, P., Porta, C., George, S., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1712126 · Cited by 4,656 · see citing works
Self-citationCox’s regression model for counting processes: A large sample study
Andersen, P. K., & Gill, R. D. (1982) · The Annals of Statistics · doi:10.1214/aos/1176345976 · Cited by 4,419 · see citing works
IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade
Ayers, M., Lunceford, J., Nebozhyn, M., Murphy, E., Loboda, A., Kaufman, D. R., Albright, A., Cheng, J. D., Kang, S. P., Shankaran, V., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci91190 · Cited by 3,788 · see citing works
Comprehensive molecular characterization of clear cell renal cell carcinoma
The Cancer Genome Atlas Research Network (2013) · Nature · doi:10.1038/nature12222 · Cited by 3,485 · see citing works
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma
Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., Berent-Maoz, B., Pang, J., Chmielowski, B., Cherry, G., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.065 · Cited by 3,448 · see citing works
Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma
Rini, B. I., Plimack, E. R., Stus, V., Gafanov, R., Hawkins, R., Nosov, D., Pouliot, F., Alekseev, B., Soulières, D., Melichar, B., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1816714 · Cited by 3,403 · see citing works
Self-citationThe pro- and anti-inflammatory properties of the cytokine interleukin-6
Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.034 · Cited by 3,212 · see citing works
Fehrenbacher, L., Spira, A., Ballinger, M., Kowanetz, M., Vansteenkiste, J., Mazieres, J., Park, K., Smith, D., Artal-Cortes, A., Lewanski, C., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00587-0 · Cited by 2,756 · see citing works
Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma
Motzer, R. J., Penkov, K., Haanen, J. B. A. G., Rini, B. I., Albiges, L. K., Campbell, M. T., Venugopal, B., Kollmannsberger, C., Négrier, S., Uemura, M., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1816047 · Cited by 2,512 · see citing works
Self-citationTumor and Microenvironment Evolution during Immunotherapy with Nivolumab
Riaz, N., Havel, J. J., Makarov, V., Desrichard, A., Urba, W. J., Sims, J. S., Hodi, F. S., Martín-Algarra, S., Mandal, R., Sharfman, W. H., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.028 · Cited by 2,401 · see citing works
The landscape of genomic alterations across childhood cancers
ICGC PedBrain-Seq Project, Gröbner, S. N., ICGC MMML-Seq Project, Worst, B. C., Weischenfeldt, J., Buchhalter, I., Kleinheinz, K., Rudneva, V. A., Johann, P. D., Balasubramanian, G. P., et al. (2018) · Nature · doi:10.1038/nature25480 · Cited by 1,572 · see citing works
McDermott, D. F., Huseni, M. A., Atkins, M. B., Motzer, R. J., Rini, B. I., Escudier, B., Fong, L., Joseph, R. W., Pal, S. K., Reeves, J. A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0053-3 · Cited by 1,260 · see citing works
Self-citationCyclooxygenase-Dependent Tumor Growth through Evasion of Immunity
Zelenay, S., van der Veen, A. G., Böttcher, J. P., Snelgrove, K. J., Rogers, N. C., Acton, S. E., Chakravarty, P., Girotti, M. R., Marais, R., Quezada, S. A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.015 · Cited by 1,123 · see citing works
Novel mutations target distinct subgroups of medulloblastoma
Robinson, G. W., Parker, M. D., Kranenburg, T. A., Lu, C., Chen, X. '., Ding, L., Phoenix, T. N., Hedlund, E., Wei, L., Zhu, X., et al. (2012) · Nature · doi:10.1038/nature11213 · Cited by 835 · see citing works
Self-citationRole of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases
Ha, H., Debnath, B., & Neamati, N. (2017) · Theranostics · doi:10.7150/thno.15625 · Cited by 788 · see citing works
OptiType: precision HLA typing from next-generation sequencing data
Szolek, A., Schubert, B., Mohr, C., Sturm, M., Feldhahn, M., & Kohlbacher, O. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu548 · Cited by 762 · see citing works
Nakano, O., Sato, M., Naito, Y., Suzuki, K., Orikasa, S., Aizawa, M., Suzuki, Y., Shintaku, I., Nagura, H., & Ohtani, H. (2001) · PubMed · Cited by 639 · see citing works
Adaptive Immune Resistance: How Cancer Protects from Immune Attack
Ribas, A. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0563 · Cited by 620 · see citing works
The Genomic Landscape of Pediatric Ewing Sarcoma
Crompton, B. D., Stewart, C., Taylor-Weiner, A. N., Alexe, G., Kurek, K. C., Calicchio, M. L., Kieżun, A., Carter, S. L., Shukla, S. A., Mehta, S. S., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-1037 · Cited by 573 · see citing works
FcγRIIB in autoimmunity and infection: evolutionary and therapeutic implications
Smith, K. G. C., & Clatworthy, M. R. (2010) · Nature reviews. Immunology · doi:10.1038/nri2762 · Cited by 542 · see citing works
Geng, L. N., Yao, Z., Snider, L. D., Fong, A. P., Cech, J. N., Young, J. M., van der Maarel, S. M., Ruzzo, W. L., Gentleman, R. C., Tawil, R., et al. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.11.013 · Cited by 459 · see citing works
HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer
Barnes, T. A., & Amir, E. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.220 · Cited by 434 · see citing works
Masiero, M., Simões, F. C., Han, H. D., Snell, C. E., Peterkin, T., Bridges, E., Mangala, L. S., Wu, S. Y., Pradeep, S., Li, D., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.06.004 · Cited by 315 · see citing works
Heery, C. R., Coyne, G. O., Madan, R. A., Cordes, L. M., Rajan, A., Rauckhorst, M., Lamping, E., Oyelakin, I., Marté, J. L., Lepone, L. M., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30239-5 · Cited by 308 · see citing works
Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma
Choueiri, T. K., Fishman, M. N., Escudier, B., McDermott, D. F., Drake, C. G., Kluger, H., Stadler, W. M., Perez-Gracia, J. L., McNeel, D. G., Curti, B., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2839 · Cited by 295 · see citing works
Self-citationChoueiri, T. K., Larkin, J., Oya, M., Thistlethwaite, F., Martignoni, M., Nathan, P., Powles, T., McDermott, D., Robbins, P. B., Chism, D. D., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30107-4 · Cited by 260 · see citing works
Self-citationRole of lipids in the metabolism and activation of immune cells
Hubler, M. J., & Kennedy, A. J. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.11.002 · Cited by 258 · see citing works
Choueiri, T. K., Figueroa, D. J., Fay, A. P., Signoretti, S., Liu, Y., Gagnon, R., Deen, K. C., Carpenter, C. F., Benson, P., Ho, T. H., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1993 · Cited by 250 · see citing works
Self-citationRoland, C. L., Lynn, K. D., Toombs, J. E., Dineen, S. P., Udugamasooriya, D. G., & Brekken, R. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007669 · Cited by 210 · see citing works
Oberg, J. A., Bender, J. G., Sulis, M. L., Pendrick, D., Sireci, A. N., Hsiao, S. J., Turk, A. T., Cruz, F. S. D., Hibshoosh, H. H., Remotti, H. E., et al. (2016) · Genome Medicine · doi:10.1186/s13073-016-0389-6 · Cited by 184 · see citing works
Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin
Coates, C. J., & Decker, H. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2326-7 · Cited by 167 · see citing works
DUX4 Suppresses MHC Class I to Promote Cancer Immune Evasion and Resistance to Checkpoint Blockade
Chew, G.-L., Campbell, A. E., Neef, E. D., Sutliff, N. A., Shadle, S. C., Tapscott, S. J., & Bradley, R. K. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.06.011 · Cited by 124 · see citing works
Choueiri, T. K., Albiges, L. K., Haanen, J. B. A. G., Larkin, J., Uemura, M., Pal, S. K., Gravis, G., Campbell, M. T., Penkov, K., Lee, J., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.15_suppl.101 · Cited by 94 · see citing works
Self-citationDUX4 Differentially Regulates Transcriptomes of Human Rhabdomyosarcoma and Mouse C2C12 Cells
Sharma, V., Harafuji, N., Belayew, A., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064691 · Cited by 74 · see citing works
Brauer, M. J., Zhuang, G., Schmidt, M., Yao, J. J., Wu, X., Kaminker, J. S., Jurinka, S. S., Kolumam, G. A., Chung, A. S., Jubb, A. M., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3635 · Cited by 61 · see citing works
Russo, L., Esposito, D. B., Lamy, F.-X., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.e13603 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445 · see citing works
HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy
Jiang, Q., Braun, D. A., Clauser, K. R., Ramesh, V., Shirole, N. H., Duke-Cohan, J. E., Nabilsi, N., Kramer, N. J., Forman, C., Lippincott, I. E., et al. (2025) · Cell · doi:10.1016/j.cell.2025.01.046 · Cited by 68 · see citing works
Self-citationJammihal, T., Saliby, R. M., Labaki, C., Soulati, H., Gallegos, J., Peris, A., McCurry, D., Yu, C., Shah, V., Poduval, D., et al. (2025) · Nature Cancer · doi:10.1038/s43018-024-00896-w · Cited by 38 · see citing works
Self-citation
- Authors
- Motzer, R. J., Robbins, P. B., Powles, T., Albiges, L., Haanen, J. B., Larkin, J., Mu, X. J., Ching, K. A., Uemura, M., Pal, S. K., Alekseev, B., Gravis, G., Campbell, M. T., Penkov, K., Lee, J. L., Hariharan, S., Wang, X., Zhang, W., Wang, J., Chudnovsky, A., di Pietro, A., Donahue, A. C., & Choueiri, T. K.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Pfizer (United States) (US)
- St Bartholomew's Hospital (GB)
- Institut Gustave Roussy (FR)
- The Netherlands Cancer Institute (NL)
- Royal Marsden NHS Foundation Trust (GB)
- Osaka University Hospital (JP)
- City Of Hope National Medical Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Asan Medical Center (KR)
- Brigham and Women's Hospital (US)
- Corresponding author
- Motzer, Robert J.
- Choueiri, Toni K.
- ORCID
- Venue
- Nature Medicine
- Published
- 2020-09-07
- Volume
- 26
- Issue
- 11
- Pages
- 1733-1741
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC8493486
- OpenAlex
- W3083058958
- Cited by
- 518
- References
- 44
- Citations by year
- 2026: 52 · 2025: 68 · 2024: 101 · 2023: 100 · 2022: 122 · 2021: 66 · 2020: 9
- FWCI
- 42.36
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pfizer
- Merck KGaA
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- advanced renal cell carcinoma, avelumab, axitinib, sunitinib, PD-L1 expression, tumor mutational burden, gene expression signatures, immunomodulatory genes, angiogenesis-related genes, HLA types, progression-free survival, predictive biomarkers, PD-1/PD-L1 blockade
- MeSH terms
- Sunitinib, Axitinib, Progression-Free Survival, Adolescent, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Renal Cell, Female, Humans, Kidney, Male, Middle Aged, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Young Adult, Transcriptome, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
