Abstract 4107
Background
Anti-PD-1 therapy is effective and durable in a subset of patients with metastatic clear cell renal cell carcinoma (mCCRCC). Previous studies have suggested that PBRM1 mutations associate with response to anti-PD-1. Here, we assessed routine, pre-treatment hematoxylin and eosin-stained (H&E) slides for features of a pre-existing immune response to tumor and tested them for an association with overall survival (OS).
Methods
We studied prospectively-collected pre-treatment biopsies from 56 patients (n = 15 treatment naïve; n = 41 previously failed at least 1 prior anti-angiogenic agent) as part of the CheckMate 009 trial (NCT01358721). H&E-stained slides were scored by two pathologists blinded to patient outcome for features of immune-related pathologic response (irPR, Cottrell, Ann Oncol 2018; Stein, Ann Oncol 2019) and necrosis. Specifically, the co-localization of moderate-high tumor infiltrating lymphocytes, plasma cells, lymphoid aggregates, neovascularization, and proliferative fibrosis was scored and compared to OS. 23 patients also had genomic data available for study.
Results
H&E evidence of a pre-existing immune response to tumor (irPR score=1 or 2) associated with improved 5-year OS (median survival undefined at 5 years vs. 16.0 months, log-rank, p = 0.006). Necrosis score alone did not associate with OS, however, a composite score (irPR minus necrosis) distinguished a population of patients with particularly poor OS following anti-PD-1 therapy (median survival 40.5 months vs. 12.3 months, log-rank, p = 0.01). Prior systemic therapy did not affect irPR or necrosis scores (p > 0.05, Fisher’s exact test). Patients positive for both an irPR score of 1 or 2 and PBRM1 mutation had significantly improved OS as compared to patients negative for both (median survival undefined vs. 7.9 months, log-rank p = 0.002).
Conclusions
Pre-treatment H&E slides can be used to predict OS in patients with mCCRCC treated with anti-PD-1 using a routine surgical pathology workflow. Early evidence suggests that the combination of irPR scoring with genomic testing for PBRM1 may further stratify the predictive ability of these assessments beyond either individual approach alone.
Clinical trial identification
NCT01358721.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
NIH T32 CA193145.
Disclosure
S. Signoretti: Advisory / Consultancy: AstraZeneca/MedImmune, Merck, AACR, NCI; Research grant / Funding (self): AstraZeneca, Exelixis, Bristol-Myers Squibb; Licensing / Royalties: Biogenex Laboratories. M. Sznol: Advisory / Consultancy: Bristol-Myers Squibb, Genentech/Roche, AstraZeneca-MedImmune, Novartis, Seattle Genetics, Nektar, Lilly, Biodesix, Modulate Therapeutics, Newlink Genetics, Molecular Partners, Innate Pharma, AbbVie, Immunocore, Genmab, Almac, Hinge, Anaeropharma, Array, G; Shareholder / Stockholder / Stock options: Amphivena, Intensity Therapeutics, Adaptive Biotechnologies, Nextcure, Actym, Torque . Y. Ishii: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. D.F. McDermott: Advisory / Consultancy: Bristol-Myers Squibb, Merck, Pfizer, Novartis, Eisai, Exelixis, Array BioPharma, Alkermes, Inc., Jounce Therapeutics, X4 Pharmaceuticals, Peloton Therapeutics, EMD Serono and Genentech BioOncology, Eli Lilly; Research grant / Funding (self): Bristol-Myers Squibb, Prometheus Laboratories, Merck, Genentech, Pfizer, Exelixis, Novartis, X4 Pharmaceuticals, Alkermes, Inc. and Peloton. T.K. Choueiri: Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Takeda; Honoraria (self), Honoraria (institution): AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, NCCN,; Advisory / Consultancy: AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Heron Therapeutics, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, A. J.M. Taube: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.
Resources from the same session
5877 - Efficacy of anti-PD(L)1 treatment in patients with metastatic urothelial cancer based on mRNA- and protein- based PD-L1 determination: Results from the multicentric, retrospective FOsMIC trial
Presenter: Jonas Jarczyk
Session: Poster Display session 3
Resources:
Abstract
5204 - A differential bladder microbiota composition is associated with tumor grade in bladder cancer.
Presenter: Monica Parra-Grande
Session: Poster Display session 3
Resources:
Abstract
4904 - Molecular characterization of metastatic urothelial carcinoma (mUC) in prior or current smokers (PCS) vs non-smokers (NS)
Presenter: Victor Sacristan Santos
Session: Poster Display session 3
Resources:
Abstract
5370 - Evaluation of different diagnostic methods for identification of FGFR alteration in advanced urothelial carcinomas: Proficiency Results based on multiple RNA extraction kits and mutation detection methods
Presenter: Veronika Weyerer
Session: Poster Display session 3
Resources:
Abstract
2579 - Title: Genomic characterization of non-schistosomiasis-related squamous cell carcinoma (NSR-SCC) of the urinary bladder: a retrospective study of potential prognostic and predictive biomarkers
Presenter: Esmail Al-ezzi
Session: Poster Display session 3
Resources:
Abstract
2203 - TiNivo: Tivozanib combined with nivolumab results in prolonged progression free survival in patients with metastatic renal cell carcinoma (mRCC). Final Results.
Presenter: Philippe Barthelemy
Session: Poster Display session 3
Resources:
Abstract
4712 - First-Line Pembrolizumab (pembro) Monotherapy for Advanced Non‒Clear Cell Renal Cell Carcinoma (nccRCC): Updated Follow-Up for KEYNOTE-427 Cohort B
Presenter: Cristina Suárez
Session: Poster Display session 3
Resources:
Abstract
2091 - First-Line Pembrolizumab (pembro) Monotherapy in Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Updated Follow-Up For KEYNOTE-427 Cohort A
Presenter: James Larkin
Session: Poster Display session 3
Resources:
Abstract
2368 - Association Between Depth of Response and Overall Survival: Exploratory Analysis in Patients With Previously Untreated Advanced Renal Cell Carcinoma (aRCC) in CheckMate 214
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract
6008 - Quality of life in previously untreated patients with advanced renal cell carcinoma (aRCC) in CheckMate 214: updated results
Presenter: David Cella
Session: Poster Display session 3
Resources:
Abstract