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
5517 - Molecular fingerprinting in breast cancer (BC) screening using Quantum Optics (QO) technology combined with an artificial intelligence (AI) approach applying the concept of “molecular profiles at n variables (MPnV)”: a prospective pilot study.
Presenter: Jean-Marc Nabholtz
Session: Poster Display session 3
Resources:
Abstract
2152 - Inferring the correlation between incidence rates of melanoma and the average tumor-specific epitope binding ability of HLA class I molecules in different populations
Presenter: Istvan Miklos
Session: Poster Display session 3
Resources:
Abstract
4382 - Thermal Liquid Biopsy as a Valuable Tool in Lung Cancer Screening Programs
Presenter: Alberto Rodrigo
Session: Poster Display session 3
Resources:
Abstract
2465 - Towards a screening test for cancer by circulating DNA analysis
Presenter: Rita Tanos
Session: Poster Display session 3
Resources:
Abstract
3788 - Evaluation of a successful launch of the MammaPrint and BluePrint NGS kit
Presenter: Leonie Delahaye
Session: Poster Display session 3
Resources:
Abstract
3863 - Analysis of prognostic factors on overall survival in elderly women treated for early breast cancer using data mining and machine learning
Presenter: Pierre Heudel
Session: Poster Display session 3
Resources:
Abstract
1993 - Circulating tumor cell detection in epithelial ovarian cancer using dual-component antibodies targeting EpCAM and FRα
Presenter: Na Li
Session: Poster Display session 3
Resources:
Abstract
4281 - CEUS of the breast: Is it feasible in improved performance of BI-RADS evaluation of critical breast lesions?——A multi-center prospective study in China
Presenter: Jun Luo
Session: Poster Display session 3
Resources:
Abstract
2268 - Classification of abnormal findings on ring-type dedicated breast PET for detecting breast cancer
Presenter: Shinsuke Sasada
Session: Poster Display session 3
Resources:
Abstract
4035 - Prediction of benign and malignant breast masses using digital mammograms texture features
Presenter: Cui Yanhua
Session: Poster Display session 3
Resources:
Abstract