Abstract 3275
Background
MicroRNAs (miRNAs) are promising biomarkers in ovarian cancer. Their kinetics during treatment might be useful for monitoring disease burden, and guiding treatments in patients treated with neoadjuvant chemotherapy and interval debulking surgery (IDS).
Methods
Serial blood samples of patients enrolled in the randomized phase II CHIVA trial, comparing neo-adjuvant carboplatin-paclitaxel +/- nintedanib (NCT01583322), were investigated to assess the kinetics of 11 relevant miRNAs compared to CA125 kinetics, using C-index & survival tests for predictive and prognostic values. MiRNAs were extracted and quantified by qRT-PCR. The selection of the final 11 miRNAs was based on the expression levels found with a large explorative panel of 84 miRNAs in 8 patients, and on the literature: miR-15b-5p, miR-16-5p, miR-20a-5p, miR-21-5p, miR-93-5p, miR-122-5p, miR-150-5p, miR-195-5p, miR-200b-3p, miR-148b-5p and miR-34a-5p.
Results
756 serial blood samples done every 3 weeks from 119 patients were analyzed for a total of 8172 miRNA assays, and 1299 CA-125 values. About 82% of miRNA concentrations were above the limits of quantification. The time courses of the miRNAs expressions were highly heterogeneous, and were not parallel with the CA-125 time changes. The miRNAs kinetics during treatment were not found associated with disease bulk changes, RECIST tumor response, or cytoreductive surgery outcomes (optimal vs non-optimal IDS). However, for 6 of them (miR-15b-5p; miR-16-5p; miR-20a-5p; miR-21-5p; miR-93-5p; and miR-195-5p), significant increases at disease progressions were found (median 40%). Decreases of miR-34a-5p and miR-93-5p were associated with PFS benefit (13.7 vs 24.8 months; p = 0.009) and OS benefits (34.3 months vs Not reached; p < 0.001), respectively, using univariate tests.
Conclusions
The longitudinal kinetics of miRNA expressions during neo-adjuvant treatment in ovarian cancer patients were inconsistent, and were not found to be associated with tumor burden changes. Although some prognostic value could be discussed, no predictive value regarding tumor responses or IDS quality could be identified.
Clinical trial identification
EudraCT: 2011-006288-23.
Editorial acknowledgement
Legal entity responsible for the study
ARCAGY-GINECO.
Funding
Boehringer Ingelheim.
Disclosure
I.L. Ray-Coquard: Honoraria (self): AstraZeneca; Honoraria (self): Clovis; Honoraria (self): Tesaro; Honoraria (self): Pharma Mar; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: pharma Mar; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): MSD; Travel / Accommodation / Expenses: AstraZeneca. J. Florence: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Sanofi; Research grant / Funding (institution): BMS; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: BMS. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. N. Raban: Travel / Accommodation / Expenses: Roche. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche. J. Alexandre: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Novartis. A. Leary: Advisory / Consultancy: Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: Gamamab; Advisory / Consultancy: Gridstone; Advisory / Consultancy: Seattle Genetics; Travel / Accommodation / Expenses: Clovis; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
2108 - Biomarker analyses of ramucirumab in patients with platinum refractory urothelial cancer from RANGE, a global, randomized, double-blind, phase 3 study.
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3090 - Comparison of Immuno-Oncology (IO) Biomarkers in Adenocarcinoma (ACB), Urothelial Carcinoma (UCB) and Squamous Cell Carcinoma (SCCB) of the Bladder, with interim results from PURE01
Presenter: Daniele Raggi
Session: Poster Display session 3
Resources:
Abstract
5211 - Potential role of a clinical, taxonomical classification and RNA expression integrated signature to predict response to neoadjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC) patients
Presenter: Albert Font
Session: Poster Display session 3
Resources:
Abstract
3206 - Hyperphosphatemia due to Erdafitinib (a Pan-FGFR Inhibitor) and Anti-tumor Activity Among Patients (Pts) with Advanced Urothelial Carcinoma (UC)
Presenter: Scott Tagawa
Session: Poster Display session 3
Resources:
Abstract
3110 - Prognostic role of FGFR Mutations and FGFR mRNA expression in metastatic urothelial cancer treated with anti-PD(L1) inhibitors in first and second line setting
Presenter: Florian Roghmann
Session: Poster Display session 3
Resources:
Abstract
3564 - Circulating tumour DNA (ctDNA) utility as a biomarker for metastatic urothelial carcinoma (mUC)
Presenter: Jean-Michel Lavoie
Session: Poster Display session 3
Resources:
Abstract
2760 - Comparative analysis of tumor mutational burden (TMB) prediction methods and its association with determinants of the tumor immune microenvironment of urothelial bladder cancer (UBC)
Presenter: Markus Eckstein
Session: Poster Display session 3
Resources:
Abstract
2513 - The Immunoscore in patients with urothelial carcinoma treated with neoadjuvant chemotherapy: clinical significance for pathological response and survival
Presenter: Elise Nassif
Session: Poster Display session 3
Resources:
Abstract
2835 - Genomic analysis of urothelial cancer and associations with treatment choice and outcome
Presenter: David Sarid
Session: Poster Display session 3
Resources:
Abstract
5763 - cfDNA is an acceptable but insufficient means of characterizing FGFR3 mutation in patients with metastatic urothelial cancer (mUC)
Presenter: Sumanta Pal
Session: Poster Display session 3
Resources:
Abstract