Found 1 Presentation For Request "1470P"
1470P - Transcriptomic signature and immune infiltrate in metastatic collecting duct renal cell carcinoma patients treated with first-line cabozantinib: Results of exploratory endpoints from BONSAI trial (Meeturo 2)
- Elena Verzoni (Milan, Italy)
Abstract
Background
The prospective phase II BONSAI trial (n=25; NCT03354884) met its primary endpoint demonstrating cabozantinib effects in untreated metastatic collecting duct carcinoma (mCDC). We aimed at investigating if baseline mCDC transcriptome is associated with outcome and/or predictive immune signatures.
Methods
FFPE samples from 18 mCDC patients from BONSAI trial were sequenced and the data processed with
Results
A 22-gene signature (BONSAI) clusters patients into a first group (n=6) with increased expression of 19/22 genes (BONSAIhigh) and longer PFS and OS, and a second group (n=12) with opposite expression trend associated with disease progression. BONSAIhigh patients exhibit best response rate to cabozantinib, while no clear association with metastasis localization, tumor mutational burden and LOH state is observed. BONSAIhigh tumors display enrichment of the predictive “angiogenesis” and “T-cell immunity” IMmotion150 trial (McDermott 2018). Conversely tumors from BONSAIlow patients are enriched in CDC-specific gene signature (Gargiuli 2021), myeloid genes associated with therapy resistance and poor outcome, as well as specific immunosuppressive signature linked to myeloid derived suppressor cells (MDSC) activity in progressive clear-cell renal carcinoma (ccRCC; Rinchai 2021).
Conclusions
mCDC is featured by a prognostic signature associating T cell immunity and angiogenesis with good clinical outcome and sensitivity to cabozantinib, differently from ccRCC. MDSC signatures linked with drug resistance and poor prognosis may warrant using myeloid-targeting drugs to achieve disease control. The study of blood MDSC of these patients is ongoing and will provide insights of role of MSDC in mCDC. A further validation of this signature will be performed in the ongoing CICERONE trial.
Clinical trial identification
NCT03354884.
Legal entity responsible for the study
The authors.
Funding
Ipsen.
Disclosure
E. Verzoni: Other, Personal, Advisory Board: MSD; Other, Personal, Speaker’s Bureau: Eisai, Pfizer; Other, Personal, Invited Speaker: Ipsen. All other authors have declared no conflicts of interest.