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Proffered Paper - GU, non prostate 1

699O - Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma (UC): Association between clinical outcomes and exploratory biomarkers

Date

19 Sep 2020

Session

Proffered Paper - GU, non prostate 1

Presenters

Srikala Sridhar

Citation

Annals of Oncology (2020) 31 (suppl_4): S550-S550. 10.1016/annonc/annonc274

Authors

S. Sridhar1, T.B. Powles2, Y. Loriot3, J. Bellmunt4, C.N. Sternberg5, D.P. Petrylak6, R. Tambaro7, L.M. Dourthe8, C. Alvarez-Fernandez9, M. Aarts10, X.J. Mu11, K.A. Ching11, J. Pu12, S. Roychoudhury13, C.B. Davis14, A. di Pietro15, P. Grivas16

Author affiliations

  • 1 Division Of Medical Oncology, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 2 Medical Oncology, Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew’s Hospital, EC1A 7BE - London/GB
  • 3 Medical Oncology, Institut Gustave Roussy, INSERMU981, Université of Paris Saclay, 94805 - Villejuif/FR
  • 4 Medical Oncology, Beth Israel Deaconess Medical Center; Harvard Medical School, 2115 - Boston/US
  • 5 Hematology/oncology, Weill Cornell Medicine, 10021 - New York/US
  • 6 Medical Oncology, Yale Cancer Center, 6520 - New Haven/US
  • 7 Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS Fondazione Giovanni Pascale, 80131 - Naples/IT
  • 8 Medical Oncology, Centre de Radiothérapie - Clinique Sainte Anne, 67000 - Strasbourg/FR
  • 9 Medical Oncology, Hospital Universitario Central de Asturias, 33011 - Oviedo/ES
  • 10 Medical Oncology, Maastricht University Medical Center, 6221 JK - Maastricht/NL
  • 11 Computational Biology, Oncology Research And Development, Pfizer, 92121 - La Jolla/US
  • 12 Statistics, Global Biometrics And Data Management, Pfizer, 92121 - La Jolla/US
  • 13 Biostatistics, Global Biometrics And Data Management, Pfizer, 07934 - Peapack/US
  • 14 Translational Oncology, Pfizer, 92121 - La Jolla/US
  • 15 Immuno-oncology, Pfizer SRL, 04100 - Milan/IT
  • 16 Department Of Medicine, Division Of Medical Oncology, University of Washington; Fred Hutchinson Cancer Research Center, 98109-4405 - Seattle/US
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Abstract 699O

Background

In the phase 3 JAVELIN Bladder 100 trial (NCT02603432), avelumab (anti–PD-L1 IgG1 antibody) 1L maintenance + BSC significantly prolonged overall survival (OS) vs BSC alone in patients (pts) with advanced UC without disease progression with 1L induction chemotherapy in all randomized pts and pts with PD-L1+ tumors. We report exploratory biomarker analyses.

Methods

Tumor biopsies were collected prior to randomization. Tumor analyses included PD-L1 (Ventana SP263 assay) and CD8 immunohistochemistry, whole-exome sequencing (including FCGR2A and FCGR3A genotypes), whole-transcriptome sequencing, and T-cell receptor (TCR) sequencing. Analyses of peripheral blood included baseline C-reactive protein (CRP) level and neutrophil:lymphocyte ratio (NLR) as well as TCR sequencing before and on treatment. Associations between OS or progression-free survival and biomarkers were evaluated using the Cox proportional hazards model. Hazard ratios and nominal p values were reported, and no multiplicity adjustments were made (5% level for statistical significance).

Results

Increased OS benefit with avelumab 1L maintenance + BSC vs BSC alone was positively associated with CD8+ T cells in the invasive margin or tumor center, high tumor mutation burden, and tumor gene expression signatures of innate and adaptive immune response. Increased OS benefit was also positively associated with the number of FCGR2A/FCGR3A alleles encoding high-affinity Fcγ receptors for IgG1. OS benefit with avelumab was negatively associated with tumor epithelial cell gene signatures, mutations affecting fibroblast growth factor receptor signaling, CRP, and NLR. In pts with elevated immune gene expression signatures, lower TGFb expression was associated with greater OS benefit with avelumab. Further analyses will be presented, including outcomes by exploratory PD-L1 cutoffs in tumor vs immune cells.

Conclusions

OS benefits of avelumab 1L maintenance in pts with advanced UC are positively associated with biomarkers of immune activity and negatively associated with biomarkers of tumor homeostasis and chronic inflammation.

Clinical trial identification

NCT02603432.

Editorial acknowledgement

Medical writing support was provided by Abhijith Thippeswamy of ClinicalThinking (Hamilton, NJ, USA) and funded by Pfizer and Merck KGaA, Darmstadt, Germany.

Legal entity responsible for the study

Pfizer.

Funding

This study was sponsored by Pfizer, and is part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany.

Disclosure

T.B. Powles: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genetech/Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Research to Practice; Honoraria (self), Travel/Accommodation/Expenses: Ferring; Honoraria (self): Gerson Lehrman Group; Honoraria (self): Janssen Research & Development. Y. Loriot: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Honoraria (self): Sanofi; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics. J. Bellmunt: Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genetech; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck. C.N. Sternberg: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Medscape; Advisory/Consultancy: UroToday; Advisory/Consultancy: Astellas Pharma; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Genzyme; Research grant/Funding (institution): Aragon Pharmaceuticals; Research grant/Funding (institution): Array BioPharma; Research grant/Funding (institution): Aveo; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Boehringer Ingelhein; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): Myovant Sciences; Research grant/Funding (institution): Nektar. S. Sridhar: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Astellas. D.P. Petrylak: Advisory/Consultancy, Research grant/Funding (institution): Ada Cap (Advanced Accelerator Applications); Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Bicycle Therapeutics; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy: Exelixis; Research grant/Funding (institution): Endocyte; Advisory/Consultancy: Incyte; Advisory/Consultancy: Janssen; Research grant/Funding (institution): Genetech; Research grant/Funding (institution): Innocrin; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Pharmacyclics; Research grant/Funding (institution): Progenies; Advisory/Consultancy, Research grant/Funding (institution): Roche Laboratories; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Sanofi Aventis; Advisory/Consultancy: Urogen; Shareholder/Stockholder/Stock options, Ownership Interest/Investment: Bellicum; Shareholder/Stockholder/Stock options, Ownership Interest/Investment (Sold 10/2019): Tyme. L.M. Dourthe: Honoraria (self), Advisory/Consultancy: Astellas ; Honoraria (self), Advisory/Consultancy: Bayer; Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer. C. Alvarez-Fernandez: Advisory/Consultancy: Ipsen; Advisory/Consultancy: Boehringer Ingelheim; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Astellas. X.J. Mu: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. K.A. Ching: Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Pfizer. J. Pu: Travel/Accommodation/Expenses, Full/Part-time employment: Roche; Full/Part-time employment: Pfizer. S. Roychoudhury: Full/Part-time employment: Pfizer. C.B. Davis: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. A. di Pietro: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. P. Grivas: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Biocept; Research grant/Funding (institution): Bavarian Nordic; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational unbranded activity with Bristol-Myers Squibb (2017): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Clovis Oncology; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Driver; Research grant/Funding (institution): Debiopharm; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: EMD Serono; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Exelixis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Foundation Medicine; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Heron Therapeutics; Research grant/Funding (institution): Immunomedics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Mirati Therapeutics; Research grant/Funding (institution): Oncogenex; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: QED Therapeutics; Honoraria (institution): KureIT; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genzyme. All other authors have declared no conflicts of interest.

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