Abstract 741P
Background
Long-term disease-free survival (LT-S) in pts with advanced high grade epithelial OC is poorly described. We recently reported that the 5yr DFS rate was <3% for pts with stage III/IV OC enrolled in 3 large 1st line trials (ESMO 2020). VIVROVAIRE enrolled LT-S OC pts (median DFS:6 yrs) regardless of stage and grade. Here we aimed to characterize the subset in VIVROVAIRE with LT-S and poor prognostic features (stage III/IV and high grade) and compare their immune profile to stage III/IV OC tumors from a neoadjuvant trial (CHIVA) with shorter survival (ST-S).
Methods
Tumors were centrally reviewed by an expert pathologist to confirm histology and grade. Staining for CK, CD3, CD8, FOXP3 was performed on the LT-S VIVROVAIRE tumors and compared to the control ST-S tumors from CHIVA (N=123). Cells were quantified in number/mm2 and the ratio of effector to suppressor (CD8/FOXP3) calculated.
Results
68 high grade (serous, endometrioid or poorly differentiated) OC tumors with LT-S were identified including 28 stage I/II (median DFS: 52mo) and 37 stages III/IV (mDFS: 59mo), 3 NA. Within the LT-S cohort, Stage I/II had fewer CD8+ (median 32 vs 85; p=0.02) and FOXP3+ cells (median 3.5 vs 12; p=0.007) compared to Stage III/IV, however there was no difference in the CD8/FOXP3 ratio in localized vs advanced stage LT-S. We next compared the immune profile of stage III/IV LT-S to the ST-S. Median DFS in the ST-S Stage III/IV was 15mo, representative of an all-comer population with advanced stage OC in the pre-PARP inhibitor era. There was no significant difference in the total number of CD8+ T cells, however Stage III/IV LT-S had significantly fewer FOXP3+ cells (12 vs 29; p=0.02) and a much more favorable effector to suppressor cell ratio (median CD8/FOXP3= 11 vs 5; p=0.007) compared to ST-S.
Conclusions
We describe a unique cohort of OC pts with exceptional survivorship (median DFS of 5yrs) despite poor prognostic features (high grade and stage III/IV). A favorable effector/suppressor balance may contribute to their improved outcomes suggesting that targeting T-regulatory cells should be explored. Further studies are ongoing to decipher the immuno-genomic features associated with prolonged remission.
Clinical trial identification
NCT02323568.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Canceropole (EMERGENCE).
Disclosure
O. Tredan: Financial Interests, Personal, Licensing Fees: Roche; Financial Interests, Personal, Licensing Fees: MSD; Financial Interests, Personal, Licensing Fees: AstraZeneca; Financial Interests, Personal, Licensing Fees: Novartis; Financial Interests, Personal, Licensing Fees: Pfizer; Financial Interests, Personal, Licensing Fees: Lilly; Financial Interests, Personal, Licensing Fees: Seagen; Financial Interests, Personal, Licensing Fees: Daiichi; Financial Interests, Personal, Licensing Fees: Eisai; Financial Interests, Personal, Licensing Fees: Pierre fabre; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: BMS. E. Kalbacher: Financial Interests, Personal and Institutional, Advisory Board: GSK; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: Roche; Financial Interests, Personal and Institutional, Advisory Board: Leopharma; Financial Interests, Personal and Institutional, Advisory Board: Bayer; Financial Interests, Personal and Institutional, Advisory Board: Sanofi; Financial Interests, Personal and Institutional, Advisory Board: Pharmamar. N. Dohollou: Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Research Grant: Boehringer; Financial Interests, Personal, Expert Testimony: Daiichi; Financial Interests, Personal, Research Grant: Genomic Health; Financial Interests, Personal, Expert Testimony, Research grant: Lilly; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Expert Testimony, Research grant: Roche; Financial Interests, Personal, Expert Testimony: Seagen. P. Pautier: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Clovis; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Pharmamar; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Roche. A. Leary: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Biocad; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Ability. All other authors have declared no conflicts of interest.