Abstract CT188: IMmotion151: updated overall survival (OS) and exploratory analysis of the association of gene expression and clinical outcomes with atezolizumab plus bevacizumab vs sunitinib in patients with locally advanced or metastatic renal cell carcinoma (mRCC)
Authors: Rini Brian I. , Atkins Michael B. , Escudier Bernard , Powles Thomas , McDermott David F. , Alekseev Boris Y. , Lee Jae-Lyun , Stroyakovskiy Daniil , Rodriguez Cristina Suarez , De Giorgi Ugo , Donskov Frede , Mellado Begoña , Banchereau Romain , Hamidi Habib , Khan Omara , Craine Veronica , Huseni Mahrukh , Flinn Nick , Dubey Sarita , Motzer Robert 
Published: July 2021

Abstract
Background: In IMmotion151 (NCT02420821), atezo (anti-PD-L1) + bev (anti-VEGF) improved PFS vs sun as 1L treatment in patients (pts) with mRCC (Rini, Lancet 2019). Gene expression analyses of baseline tumor tissue revealed 7 distinct transcriptomic clusters associated with objective response rate and PFS (Motzer, Cancer Cell 2020). Final OS, safety and association of transcriptome subsets with OS are presented.
Methods: Treatment-naive pts across prognostic risk groups were randomized 1:1 to receive atezo 1200 mg IV + bev 15 mg/kg IV q3w or sun 50 mg PO QD 4 wk on/2 wk off. Co-primary endpoints were PFS by investigator per RECIST 1.1 in PD-L1+ (≥ 1% IC) pts and OS in ITT pts. Secondary endpoints included OS in PD-L1+ pts and safety. Exploratory endpoints included biomarker analyses.
Results: In the final analysis (minimum follow-up 40 mo) with a 55% (504/915) OS event rate, atezo + bev did not show an OS benefit vs sun (Table). Treatment-related AEs (TRAEs) were observed in 92% (415/451) and 96% (430/446) of ITT pts in the atezo + bev and sun arms, and Grade 3-4 TRAEs were observed in 46% (205/451) and 56% (250/446), respectively. In exploratory biomarker analyses, sun showed an improved OS trend in tumors characterized by an angiogenic transcription profile, and atezo + bev showed improved OS trend in tumors characterized by T-effector/proliferative, proliferative or small nucleolar RNA transcription profiles (Table). When the latter 3 groups were combined, atezo + bev resulted in better OS than sun (HR, 0.70; 95% CI: 0.50, 0.98).
Conclusions: Overall, in this final analysis, no OS improvement with atezo + bev vs sun was seen. The safety of atezo + bev was consistent with the known safety profile of each component. Biomarker studies generated hypotheses for which pt subgroups are most likely to benefit from combined anti-VEGF + anti-PD-L1 therapy.
PopulationCluster transcription profileHR (95% CI)P valueMedian OS (atezo + bev)Median OS (sun)ITT (n=915)NA0.91 (0.76, 1.08)a0.27b36.135.3PD-L1+ (n=362)NA0.85 (0.64, 1.13)a0.2638.731.6Cluster 1 (n=98)Angiogenic/stromal0.94 (0.52, 1.72)_NR48.2Cluster 2 (n=245)Angiogenic1.32 (0.91, 1.91)_46.2NRCluster 3 (n=156)Complement/Ω-oxidative0.99 (0.64, 1.54)_35.036.6Cluster 4 (n=116)T-effector/proliferative0.66 (0.41, 1.06)_38.723.3Cluster 5 (n=74)Proliferative0.66 (0.39, 1.12)_21.715.5Cluster 6 (n=106)Stromal/proliferative0.90 (0.57, 1.40)_15.912.7Cluster 7 (n=28)snoRNANC_NR42.1Gene expression clusters 4 (T-effector/proliferative) + 5 (proliferative) + 7 (snoRNA) (n=218)_0.70 (0.50, 0.98)_35.421.2aPts were stratified by MSKCC Risk Score (good vs intermediate vs poor), liver metastases (yes vs no) and PD-L1 IHC status (&lt; 1% vs ≥ 1% PD-L1 expression on IC; SP142 IHC assay).bThe pre-specified α boundary was 0.0203.atezo, atezolizumab; bev, bevacizumab; HR, hazard ratio; IC, tumor-infiltrating immune cells; IHC, immunohistochemistry; ITT, intention to treat; MSKCC, Memorial Sloan Kettering Cancer Center; NA, not applicable; NC, not calculated; NR, not reported; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression free survival; snoRNA, small nucleolar RNA; sun, sunitinib.
Citation Format: Brian I. Rini, Michael B. Atkins, Bernard Escudier, Thomas Powles, David F. McDermott, Boris Y. Alekseev, Jae-Lyun Lee, Daniil Stroyakovskiy, Cristina Suarez Rodriguez, Ugo De Giorgi, Frede Donskov, Begoña Mellado, Romain Banchereau, Habib Hamidi, Omara Khan, Veronica Craine, Mahrukh Huseni, Nick Flinn, Sarita Dubey, Robert Motzer. IMmotion151: updated overall survival (OS) and exploratory analysis of the association of gene expression and clinical outcomes with atezolizumab plus bevacizumab vs sunitinib in patients with locally advanced or metastatic renal cell carcinoma (mRCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT188.