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
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