Abstract 1475P
Background
mRCC treatment has expanded to include several ICIs and combinations with targeted kinase inhibitors. However, only clinical criteria has been validated to predict for ICI treatment responses. We previously described a highly sensitive CTC assay with multivalent binding, e-selectin induced cell rolling, and multiple antibody ligands. We prospectively evaluated whether CTC change would predict for ICI response in mRCC.
Methods
Patients with mRCC treated with nivolumab (nivo) alone or with ipilimumab (ipi) or cabozantinib were enrolled prospectively at Duke Cancer Institute. Peripheral blood specimens were obtained from patients at baseline, weeks (wks) 4 and 12 during treatment, and upon disease progression. A dendrimer-based assay functionalized with antibodies against EpCAM, CA-9, MET, and EGFR captured CTCs, identified as DAPI+/CD45-/CK+ cells. Based on response assessment of patients after treatment and the CTC change between baseline and wk 4, we categorized CTC changes as concordant when CTC numbers decreased with Partial Response (PR) or Complete Response (CR), or stabilized or increased with Stable Disease (SD) or Progression Disease (PD); or discordant when CTCs increased with PR or CR, or decreased with SD or PD.
Results
32 patients were enrolled, with 25 patients having both analyzable baseline and wk 4 samples. Baseline demographics included median age 63 (27-83), 88% male, 88% Caucasian, 60% treated with ipi-nivo, and 56% first-line, 36% 2nd/3rd line, and 8% >3 prior treatments. CTCs were detected at baseline (median 19.8 CTCs/mL, IQR 4.9-59.9 CTCs/mL) and wk 4 (median 11.9 CTCs/mL, IQR 1.7-86 CTCs/mL). Baseline-wk 4 CTC changes were found concordant with ICI responses in 72% (18/25) of all patients, including 73% (8/11) PD, 83% (5/6) SD, 50% (3/6) PR and 100% (2/2) CR. Most 75% (6/8) patients with CR/PR had >75% decrease in baseline-wk 4 CTCs, with some variability.
Conclusions
Our study shows changes in CTCs captured with MET, CA-IX, EGFR and EpCAM may be used for real-time monitoring of ICI responses in patients with mRCC. With larger samples for validation, CTCs may be used as a tumor biomarker to predict ICI responses.
Clinical trial identification
NCT02978118.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Duke Cancer Institute Center for Prostate and Urologic Cancers.
Disclosure
T. Zhang: Financial Interests, Personal, Advisory Board: Merck, Exelixis, Sanofi-Aventis, Janssen, AstraZeneca, Pfizer, Amgen, BMS, Pharmacyclics, Seagen, Calithera, Dendreon, QED Therapeutics, Eisai, Aveo, Bayer, Eli Lilly; Financial Interests, Personal, Other, Consulting: MJH Associates, Vanaiam, Aptitude Health, PeerView, Clinical Care Options; Financial Interests, Institutional, Invited Speaker: Novartis, Merrimack, AbbVie, Merck, Regeneron, Mirati Therapeutics, Janssen, AstraZeneca, Pfizer, Astellas; Financial Interests, Institutional, Research Grant: OmniSeq, PGDx; Non-Financial Interests, Advisory Role, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Advisory Role, Scientific Advisory Board: KCCure; Non-Financial Interests, Advisory Role: Myrovlytis Trust. A.J. Armstrong: Financial Interests, Personal, Advisory Board: BMS, Merck, Pfizer, AstraZeneca, Forma, Exelixis, Myovant, Clovis, Epic Sciences, Janssen, Bayer; Financial Interests, Institutional, Principal Investigator: BMS, Merck, Pfizer, AstraZeneca, Exelixis, Myovant, Dendreon, Clovis, Genentech Roche, Amgen, Janssen, Bayer; Financial Interests, Institutional, Research Grant: Forma. D.J. George: Financial Interests, Personal, Other, Consultant: Advanced Accelerator Applications SA/Novartis, Aveo Pharmaceuticals, Eisai, IdeoOncology, Merck Sharp & Dohme, Myovant Sciences, Inc., Propella Therapeutics, RevHealth, LLC, Seattle Genetics, WebMD, Xcures; Financial Interests, Personal, Other, Sr. Editor: American Association for Cancer Research; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board, CAPI-281 Steering Committee member: AstraZeneca; Financial Interests, Personal, Invited Speaker, and Consultant: Bayer H/C Pharmaceuticals, Exelixis, Inc.; Financial Interests, Personal, Other, Consultant/IDMC member: Janssen Pharmaceuticals; Financial Interests, Personal, Other, Contributor: Medscape Education; Financial Interests, Personal, Other, Honorarium, Consultant: Michael J Hennessey Associates; Financial Interests, Personal, Other, Co-Editor-in-Chief: Millennium Medical Publishing, Clinical Advances in Hematology & Oncology; Financial Interests, Personal, Other, Steering Committee member: NCI Genitourinary (Leidos biomedical Research); Financial Interests, Personal, Other, Consultant, Steering Committee member, Honorarium: Pfizer; Financial Interests, Personal, Other, Consultant, Speaker, Honorarium: Sanofi; Financial Interests, Personal, Other, Honorarium: UroGPO; Financial Interests, Personal, Other, Honorarium, Travel Accommodations: UroToday; Financial Interests, Personal, Expert Testimony: WilmerHale Attorneys; Financial Interests, Institutional, Funding: Astellas, AstraZeneca, Bristol Myers Squibb, Calithera, Exelisix, Janssen Pharmaceuticals, Novartis, Pfizer, Sanofi. A.Z. Wang: Financial Interests, Personal, Leadership Role: Capio Biosciences, Archimmune Therapeutics; Financial Interests, Personal, Ownership Interest: Capio Biosciences, Archimmune Therapeutics. S. Hong: Financial Interests, Personal, Leadership Role: Capio Biosciences; Financial Interests, Personal, Advisory Board: Dongkook Pharmaceuticals, BioView, Ltd.; Financial Interests, Institutional, Research Grant: Capio Biosciences, Dongkook Pharmaceuticals, Werfen; Financial Interests, Personal, Ownership Interest: Capio Biosciences. All other authors have declared no conflicts of interest.