Abstract 2108
Background
RANGE previously reported positive progression-free survival1 and a trend towards improved overall survival (OS)2 in ramucirumab (RAM) treated patients. Exploratory biomarker analysis of efficacy by programmed death-ligand 1 (PD-L1) expression revealed a hazard ratio (HR) for OS of 0.519, p = 0.0048 in patients with a PD-L1 combined positive score (CPS)≥10 compared to HR of 0.999, p = 0.9955 in patients with a PD-L1 CPS<10. We aim to understand prognostic and predictive factors related to survival outcomes in RANGE, and to identify patients who may benefit from RAM therapy using PD-L1 immunohistochemistry and gene expression analysis, defining molecular subtypes, and tumour microenvironment signatures.
Methods
Archival tumour specimens that met assay stability requirements (238/530 ITT patients in RANGE) were analyzed with the 22C3 PD-L1 antibody with CPS based on tumour cell (TC) and immune cell (IC) staining. RNA expression analysis on archival tumour tissue (394/530 ITT patients) was done by GenomeDx (RNA microarray)3. PD-L1 groups, urothelial carcinoma molecular subtypes, and immune4 and stromal phenotypes5 were determined and analyzed for association with OS outcome.
Results
Overall, RAM had the greatest improvement in OS in patients with TC ≥ 1, IC ≥ 4 or CPS≥10 PD-L1 status. OS was also more improved in patients with basal subtypes, with considerable overlap noted between basal subtypes and TC ≥ 1, IC ≥ 4, or CPS ≥10 PD-L1 status. In the subgroup with both basal/basal claudin-low subtype and CPS≥10 PD-L1 status, median OS was 9.2 months with RAM and 6.0 months with placebo (stratified hazard ratio 0.47; 95% confidence interval: 0.27-0.84, p = 0.01, n = 79).
Conclusions
Our analysis suggested significant improvement in OS in RAM treated patients with platinum refractory urothelial carcinoma, and with both basal subtype and positive PD-L1 status. References: 1Petrylak et al, Lancet 2017; 390:2266-77; 2Petrylak et al, Ann Oncol 2018; 29:viii304-5; 3Seiler et al, Eur Urol 2017; 72:544-54; 4Charoentong et al, Cell Rep 2017; 18:248-62; 5Uhlik et al Cancer Res 2016; 76:2573-86.
Clinical trial identification
NCT02426125.
Editorial acknowledgement
Lisa Cossens and Antonia Baldo of Syneos Health, funded by Eli Lilly and Company.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
T.B. Powles: Research grant / Funding (self), Personal fees: Roche; Research grant / Funding (self), Personal fees: AZ; Licensing / Royalties, Personal fees: Merck; Licensing / Royalties, Personal fees: Eli Lilly and Company; Licensing / Royalties, Personal fees: BMS; Licensing / Royalties, Personal fees: Pfizer. D.P. Petrylak: Research grant / Funding (self): Eli Lilly and Company; Licensing / Royalties, Personal fees: Bayer; Research grant / Funding (self), Licensing / Royalties, Personal fees: Bellicum; Research grant / Funding (self), Licensing / Royalties, Personal fees: Dendreon; Research grant / Funding (self), Licensing / Royalties, Personal fees: Sanofi Aventis; Research grant / Funding (self), Licensing / Royalties, Personal fees: Johnson and Johnson; Licensing / Royalties, Personal fees: Exelixis; Licensing / Royalties, Personal fees: Ferring; Research grant / Funding (self), Licensing / Royalties, Personal fees: Millineum; Licensing / Royalties, Personal fees: Medivation; Licensing / Royalties, Personal fees: Pfizer; Research grant / Funding (self), Licensing / Royalties, Personal fees: Roche Laboratories; Research grant / Funding (self), Licensing / Royalties, Personal fees: Tyme Pharmaceuticals; Research grant / Funding (self): Oncogenix; Research grant / Funding (self): Progenics; Research grant / Funding (self): Merck; Research grant / Funding (self): Agensys. R. de Wit: Licensing / Royalties: Eli Lilly and Company; Licensing / Royalties: Merck; Licensing / Royalties: Roche; Licensing / Royalties: Sanofi. K.N. Chi: Research grant / Funding (institution): Eli Lilly and Company. A. Necchi: Research grant / Funding (self), Licensing / Royalties, Non-remunerated activity/ies: Roche; Licensing / Royalties: Merck; Licensing / Royalties: AstraZeneca; Licensing / Royalties: Seattle Genetics; Licensing / Royalties: Bayer. C.N. Sternberg: Licensing / Royalties: Eli Lilly and Company; Licensing / Royalties: BMS; Licensing / Royalties: Merck/Pfizer; Licensing / Royalties: Clovis. S.A. Hussain: Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): MSD; Research grant / Funding (institution): BMS. A. Bamias: Licensing / Royalties: AstraZeneca; Licensing / Royalties: BMS; Research grant / Funding (self), Licensing / Royalties: Roche. M.S. Xia: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. E. Rasmussen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company.A. Aggarwal: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. S.R. Wijayawardana: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. K. Bell-McGuinn: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. All other authors have declared no conflicts of interest.
Resources from the same session
4614 - Predictors of Response to Checkpoint Inhibitors in Naïve and Ipilimumab-Refractory Melanoma
Presenter: Domenico Mallardo
Session: Poster Display session 3
Resources:
Abstract
2901 - IFN-γ/IL-10 ratio as predictive biomarker for response to anti-PD-1 therapy in metastatic melanoma patients
Presenter: Emilio Giunta
Session: Poster Display session 3
Resources:
Abstract
2306 - Multiplex Chromogenic Immunohistochemistry (IHC) for Spatial Analysis of Checkpoint-Positive Tumor Infiltrating Lymphocytes (TILs)
Presenter: Scott Ely
Session: Poster Display session 3
Resources:
Abstract
1678 - The role of PD-L1 expression as a predictive biomarker in advanced renal cell carcinoma: a meta-analysis of randomized clinical trials.
Presenter: Alberto Carretero-Gonzalez
Session: Poster Display session 3
Resources:
Abstract
5138 - Radiomic Features as a Non-invasive Biomarker to Predict Response to Immunotherapy in Recurrent or Metastatic Urothelial Carcinoma
Presenter: Kye Jin Park
Session: Poster Display session 3
Resources:
Abstract
5800 - Integrative combination of high-plex digital profiling techniques and cluster analysis to reveal complex immune biology in the tumor microenvironment of mesothelioma
Presenter: Carmen Ballesteros-Merino
Session: Poster Display session 3
Resources:
Abstract
5736 - Predictive factors of response to immunotherapy in 198 patients with metastatic non-microcytic lung cancer (mNSCLC): real world data from 2 university hospitals in Spain
Presenter: Juan Felipe Cordoba Ortega
Session: Poster Display session 3
Resources:
Abstract
5645 - Evaluating Lung CT Density Changes Among Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) Treated with Thoracic Radiotherapy (TRT) alone or TRT Followed by Combined Ipilimumab (IPI) and Nivolumab (NIVO).
Presenter: Kujtim Latifi
Session: Poster Display session 3
Resources:
Abstract
1540 - Immuno-oncology therapy biomarkers differences between polyoma-virus positive and negative Merkel cell carcinomas
Presenter: Zoran Gatalica
Session: Poster Display session 3
Resources:
Abstract
4538 - Can we improve patient selection for phase 1 clinical trials (Ph1) based on Immuno-Oncology score prognostic index (VIO)?
Presenter: Ignacio Matos Garcia
Session: Poster Display session 3
Resources:
Abstract