Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

We examined pre-treatment tumors from participants of the IMmotion150 trial. Biomarker analyses indicate that high angiogenesis gene expression was associated with improved PFS within the sunitinib arm, and high T-effector/IFNγ response (Teff) gene expression with longer PFS in atezolizumab + bevacizumab vs sunitinib patients. In high Teff tumors, concomitant high myeloid inflammation was associated with worse PFS in the atezolizumab monotherapy arm; adding bevacizumab to atezolizumab in this subgroup improved PFS vs atezolizumab. Molecular profiles suggest that prediction of outcomes with VEGF inhibitors and immunotherapy may be possible in mRCC, and bevacizumab may overcome myeloid inflammation-associated atezolizumab resistance.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 15 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001004183	Tumor transcriptome and whole exome sequencing data (matched tumor/normal for somatic mutation calling) along with key phenotypic information are provided for patients enrolled in the phase 2 IMmotion150 trial, assessing efficacy of atezolizumab monotherapy or combination of atezolizumab and bevacizumab versus standard of care (sunitinib) in 1L renal cell carcinoma. This data set accompanies the respective Nature Medicine publication (PMID: 29867230).	Illumina HiSeq 2500	589

Publications	Citations
Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, Fong L, Joseph RW, Pal SK, Reeves JA, Sznol M, Hainsworth J, Rathmell WK, Stadler WM, Hutson T, Gore ME, Ravaud A, Bracarda S, Suárez C, Danielli R, Gruenwald V, Choueiri TK, Nickles D, Jhunjhunwala S, Piault-Louis E, Thobhani A, Qiu J, Chen DS, Hegde PS, Schiff C, Fine GD, Powles T. Nat Med 24: 2018 749-757	607
PBRM1 loss defines a nonimmunogenic tumor phenotype associated with checkpoint inhibitor resistance in renal carcinoma. Liu XD, Kong W, Peterson CB, McGrail DJ, Hoang A, Zhang X, Lam T, Pilie PG, Zhu H, Beckermann KE, Haake SM, Isgandrova S, Martinez-Moczygemba M, Sahni N, Tannir NM, Lin SY, Rathmell WK, Jonasch E. Nat Commun 11: 2020 2135	94
Escape from nonsense-mediated decay associates with anti-tumor immunogenicity. Litchfield K, Reading JL, Lim EL, Xu H, Liu P, Al-Bakir M, Wong YNS, Rowan A, Funt SA, Merghoub T, Perkins D, Lauss M, Svane IM, Jönsson G, Herrero J, Larkin J, Quezada SA, Hellmann MD, Turajlic S, Swanton C. Nat Commun 11: 2020 3800	56
A pan-cancer analysis of PBAF complex mutations and their association with immunotherapy response. Hakimi AA, Attalla K, DiNatale RG, Ostrovnaya I, Flynn J, Blum KA, Ged Y, Hoen D, Kendall SM, Reznik E, Bowman A, Hwee J, Fong CJ, Kuo F, Voss MH, Chan TA, Motzer RJ. Nat Commun 11: 2020 4168	32
Antagonistic Inflammatory Phenotypes Dictate Tumor Fate and Response to Immune Checkpoint Blockade. Bonavita E, Bromley CP, Jonsson G, Pelly VS, Sahoo S, Walwyn-Brown K, Mensurado S, Moeini A, Flanagan E, Bell CR, Chiang SC, Chikkanna-Gowda CP, Rogers N, Silva-Santos B, Jaillon S, Mantovani A, Reis e Sousa C, Guerra N, Davis DM, Zelenay S. Immunity 53: 2020 1215-1229.e8	108
Transcriptomic signatures of tumors undergoing T cell attack. Gokuldass A, Schina A, Lauss M, Harbst K, Chamberlain CA, Draghi A, Westergaard MCW, Nielsen M, Papp K, Sztupinszki Z, Csabai I, Svane IM, Szallasi Z, Jönsson G, Donia M. Cancer Immunol Immunother 71: 2022 553-563	5
Replication stress response defects are associated with response to immune checkpoint blockade in nonhypermutated cancers. McGrail DJ, Pilié PG, Dai H, Lam TNA, Liang Y, Voorwerk L, Kok M, Zhang XH, Rosen JM, Heimberger AB, Peterson CB, Jonasch E, Lin SY. Sci Transl Med 13: 2021 eabe6201	19
PBRM1 Inactivation Promotes Upregulation of Human Endogenous Retroviruses in a HIF-Dependent Manner. Zhou M, Leung JY, Gessner KH, Hepperla AJ, Simon JM, Davis IJ, Kim WY. Cancer Immunol Res 10: 2022 285-290	9
Decoding the multicellular ecosystem of vena caval tumor thrombus in clear cell renal cell carcinoma by single-cell RNA sequencing. Shi Y, Zhang Q, Bi H, Lu M, Tan Y, Zou D, Ge L, Chen Z, Liu C, Ci W, Ma L. Genome Biol 23: 2022 87	28
Transcriptomic datasets of cancer patients treated with immune-checkpoint inhibitors: a systematic review. Kovács SA, Győrffy B. J Transl Med 20: 2022 249	33
The cuproptosis-associated 13 gene signature as a robust predictor for outcome and response to immune- and targeted-therapies in clear cell renal cell carcinoma. Yuan H, Qin X, Wang J, Yang Q, Fan Y, Xu D. Front Immunol 13: 2022 971142	20
Tumor and immune remodeling following radiotherapy in human renal cell carcinoma. Chow J, Khan A, Gaudieri M, Wasik BJ, Conway A, Soh KT, Repasky EA, Schwaab T, Wallace PK, Abrams SI, Singh AK, Muhitch JB. J Immunother Cancer 11: 2023 e006392	3
Dyskerin and telomerase RNA component are sex-differentially associated with outcomes and Sunitinib response in patients with clear cell renal cell carcinoma. Yuan H, Qin X, Yang Q, Liu L, Fang Z, Fan Y, Xu D. Biol Sex Differ 14: 2023 46	3
Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy. Schina A, Sztupinszki Z, Marie Svane I, Szallasi Z, Jönsson G, Donia M. J Immunother Cancer 11: 2023 e006941	4
Multiple instance learning to predict immune checkpoint blockade efficacy using neoantigen candidates. Lang F, Sorn P, Schrörs B, Weber D, Kramer S, Sahin U, Löwer M. iScience 26: 2023 108014	1