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.
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