Abstract 1472P
Background
Papillary Renal Cell Carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC). In silico, we identified 4 subgroups according to the proportion of immune and stromal cell populations in a preliminary study in 271 localized pRCC tumors using RNA-seq data from The Cancer Genome Atlas (TCGA), validated in independent cohort. Thus, the microenvironment of pRCC is yet to be described in a cohort of metastatic pRCC treated with systemic therapy and its association with response and outcomes to be assessed.
Methods
We performed a post-hoc analysis of the AXIPAP trial which explored axitinib in first line metastatic pRCC specifically (Negrier et al, EJC, 2020, by the GETUG collaborative group). In immunohistochemistry (IHC), the immune infiltration was analyzed by the CD8/CD3/PD-L1/CD68 staining, intra-tumoral and invasion front, and tumor-infiltrating lymphocytes scoring. The angiogenesis was analyzed by CD31 and VEGF staining.
Results
Among 38 pRCC included in our analysis, we applied unsupervised clustering from IHC staining, identifying 3 different groups of pRCC: “immunolow/Angiolow”, “Immunolow/Angiohigh” and “Immunohigh/Angiolow” groups. Only “Immunolow/Angiohigh” group (n=13) was associated to high vascular density, with more aggressive prognostic factors such as high grade (85%), Fuhrman grade 3-4 (85%), type 2 (77%), with rabdoid or sarcomatoid component (38%). The endpoints are presented in the table. As in silico analysis with localized pRCC from TCGA, the "Immunolow/Angiohigh” cluster, in this metastatic cohort, appeared to have a worse prognosis. Table: 1472P
| Endpoints | immunolow/Angiolow N = 14 (37%) | Immunolow/Angiohigh N = 13 (34%) | Immunohigh/Angiolow N = 11 (29%) | Overall cohortN = 38 |
| ORR | 14% | 31% | 18% | 22% |
| 6-month PFS | 57.1% | 61.5% | 45.7% | 55.7% |
| 6-month OS | 92.8% | 61.5% | 90.9% | 81.6% |
Conclusions
For the first time, we characterized the tumor microenvironment of metastatic pRCC treated by VEGF-TKI in prospective trial. We identified 3 different groups by using IHC clustering on immune and vascular infiltration, with different response and outcomes. These rare tumors require specific biomarkers of response. Further transcriptomics analyses and response of treatment will be presented to ESMO meeting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
ARTUR.
Disclosure
M. De Vries-Brilland: Financial Interests, Institutional, Invited Speaker: BMS, Ipsen, AAA; Financial Interests, Institutional, Advisory Role: BMS; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Institutional, Research Grant: Ipsen. G. Gravis Mescam: Financial Interests, Institutional, Advisory Board: AAA, Alliance Merck-Pfizer, Astellas, BMS, Janssen, Pfizer, Ipsen, Alliance Merck Pfizer; Financial Interests, Institutional, Invited Speaker: AAA, Amgen, Astellas, BMS, Janssen, MSD, Pfizer, Sanofi, IPSEN, Astra Zeneca, BMS; Financial Interests, Institutional, Funding: Janssen; Non-Financial Interests, Principal Investigator: Ipsen, BMS, Merck. L. Geoffrois: Financial Interests, Institutional, Advisory Role: BMS, MSD, Novartis, Ipsen, Janssen. C.M. Chevreau: Financial Interests, Personal, Advisory Board: Ipsen, BMS, LEO, MSD; Financial Interests, Institutional, Invited Speaker, only for overhead: MSD, Ipsen, Karyopharm, Exelisis. M. Gross Goupil: Financial Interests, Institutional, Advisory Role: Astellas, Janssen, Ipsen, MSD; Financial Interests, Institutional, Research Grant: MSD, BMS, Janssen, Astrazeneca, Pfizer, Roche; Financial Interests, Institutional, Other: Amgen, MSD, Roche, Pfizer, Sanofi. B. Escudier: Financial Interests, Institutional, Advisory Role: BMS, Novartis, Pfizer, Roche, Ipsen, EUSA, AVEO; Financial Interests, Institutional, Other: BMS, Pfizer; Financial Interests, Institutional, Research Grant: BMS, Novartis, AVEO, Pfizer. S. Negrier: Financial Interests, Institutional, Research Grant: Pfizer, IPSEN; Non-Financial Interests, Institutional, Other: Pfizer, BMS, Ipsen, MSD, EISAI; Financial Interests, Institutional, Other, Personal Fees: Pfizer, BMS; Financial Interests, Institutional, Other, Personnal Fees: Ipsen, Novartis, MSD, EISAI. L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, AstraZeneca, BMS, EISAI, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Pfizer, BMS, Ipsen, AVEO, AstraZeneca, MSD; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU); Non-Financial Interests, Other, Member of the Kidney Cancer Research Summit scientific committee 2021: Kidney Can; Other, Scientific Committee: BMS France. All other authors have declared no conflicts of interest.