Results of PD-L1 Analysis of Women Treated with Durvalumab in Advanced Endometrial Carcinoma (PHAEDRA)

Smith, D; Robledo, KP; Yip, S; Cummins, MM; Kok, PS; Lee, YC; Friedlander, M; Baron-Hay, S; Shannon, C; Coward, J; Beale, P; Goss, G; Meniawy, T; Lombard, J; Spurdle, AB; Andrews, J; Stockler, MR; Mileshkin, L; Antill, Y; Australia New Zealand Gynaecological Oncology Group (ANZGOG)

Author(s): Smith, D; Robledo, KP; Yip, S; Cummins, MM; Kok, PS; Lee, YC; Friedlander, M; Baron-Hay, S; Shannon, C; Coward, J; Beale, P; Goss, G; Meniawy, T; Lombard, J; Spurdle, AB; Andrews, J; Stockler, MR; Mileshkin, L; Antill, Y; Australia New Zealand Gynaecological Oncology Group (ANZGOG);
Details: Publication Year 2023-12-30,Volume 15,Issue #1,Page 254
Journal Title: Cancers
Publication Type: Research article
Abstract: Women with advanced endometrial carcinoma (EC) with mismatch repair (MMR) deficiency have improved outcomes when treated with immune checkpoint inhibitors; however, additional biomarkers are needed to identify women most likely to respond. Scores for programmed death ligand 1 (PD-L1), immunohistochemical staining of tumor (TC+), immune cells (IC+) and presence of tumor-associated immune cells (ICP) on MMR deficient (n = 34) and proficient (n = 33) EC from women treated with durvalumab in the PHAEDRA trial (ANZGOG1601/CTC0144) (trial registration number ACTRN12617000106336, prospectively registered 19 January 2017) are reported and correlated with outcome. Receiver operating characteristic (ROC) analyses and area under the ROC curve were used to determine optimal cutpoints. Performance was compared with median cutpoints and two algorithms; a novel algorithm derived from optimal cutpoints (TC+ >/= 1 or ICP >/= 10 or IC+ >/= 35) and the Ventana urothelial carcinoma (UC) algorithm (either TC+ >/= 25, ICP > 1 and IC+ >/= 25 or ICP = 1 and IC+ = 100). The cutpoint ICP >/= 10 had highest sensitivity (53%) and specificity (82%), being prognostic for progression-free survival (PFS) (p = 0.01), while the optimal cutpoints algorithm was associated with overall survival (p = 0.02); these results were not significant after adjusting for MMR status. The optimal cutpoints algorithm identified non-responders (p = 0.02) with high sensitivity (88%) and negative predictive value (92%), remaining significant after adjustment for MMR. Although MMR status had the strongest association with response, further work to determine the significance of ICP >/= 10 and the novel optimal cutpoint algorithm is needed.
Publisher: MDPI
Keywords: endometrial carcinoma; immune checkpoint inhibitors; immunohistochemistry; programmed death ligand 1; receiver operating characteristic analyses
Department(s): Medical Oncology
PubMed ID: 36612250
Publisher's Version: https://doi.org/10.3390/cancers15010254
Open Access at Publisher's Site: https://doi.org/10.3390/cancers15010254
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-08-20 06:17:56

Last Modified: 2024-08-20 06:56:39