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
2262 - Real world experience of Nivolumab therapy in Metastatic Renal Cancer patients: a 3 year multi-centre review
Presenter: Joanna Hack
Session: Poster Display session 3
Resources:
Abstract
4441 - “A pilot study of tremelimumab (treme) with or without cryoablation (cryo) in patients (pts) in metastatic renal cell carcinoma (mRCC).”
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
2613 - Lenvatinib (Len) alone or in combination with Everolimus (Eve) in heavily pretreated patients (pts) with metastatic renal cell carcinoma (mRCC) after immune checkpoint inhibitors (ICI) and VEGFR-targeted therapies: A single-institution experience
Presenter: Andrew Wiele
Session: Poster Display session 3
Resources:
Abstract
3249 - Weight loss is an underestimated adverse event with cabozantinib in patients with metastastic renal cell carcinoma (mRCC).
Presenter: Emeline Colomba
Session: Poster Display session 3
Resources:
Abstract
2405 - Impact of corticosteroids on nivolumab activity in metastatic clear cell renal cell carcinoma.
Presenter: Felix Lefort
Session: Poster Display session 3
Resources:
Abstract
4020 - Skeletal muscle loss as an adverse event during Cabozantinib treatment in patients with metastatic renal cell carcinoma
Presenter: Carolina Alves Costa Silva
Session: Poster Display session 3
Resources:
Abstract
2407 - Long term relative survival (RS) in patients with primary metastatic kidney cancer (primary mRCC): an analysis of 2,167 patients from the Austrian National Cancer Registry (ANCR).
Presenter: Monika Hackl
Session: Poster Display session 3
Resources:
Abstract
2470 - Advanced renal cell carcinoma: first results from the prospective research platform CARAT for patients with mRCC in Germany
Presenter: Peter Goebell
Session: Poster Display session 3
Resources:
Abstract
1533 - Are immune checkpoint inhibitors a valid option for papillary Renal Cell Carcinoma? Transcriptomic characterization of the immune infiltrate
Presenter: Manon De Vries-brilland
Session: Poster Display session 3
Resources:
Abstract
3367 - Treatment-Free Survival, With and Without Toxicity, as a Novel Outcome Applied to Immuno-Oncology Agents in Advanced Renal Cell Carcinoma
Presenter: Meredith Regan
Session: Poster Display session 3
Resources:
Abstract