| Title: |
Immunological biomarkers of response and resistance to treatment with cabozantinib and nivolumab in recurrent endometrial cancer |
| Authors: |
Roudko, Vladimir; Del Valle, Diane Marie; Radkevich, Emir; Kelly, Geoffrey; Hui, Xie; Patel, Manishkumar; Gonzalez-Kozlova, Edgar; Tuballes, Kevin; Streicher, Howard; Atale, Swati; Wang, Lisa; CzinCzin, Benito; Kim-Schulze, Seunghee; Wistuba, Ignacio I; Haymaker, Cara L; Al-Atrash, Gheath; Manyam, Ganiraju; Zhang, Jianjun; Thompson, Ryan; Suarez-Farinas, Mayte; Lheureux, Stephanie; Gnjatic, Sacha |
| Contributors: |
National Cancer Institute; National Center for Advancing Translational Sciences; Conquer Cancer Foundation |
| Source: |
Journal for ImmunoTherapy of Cancer ; volume 13, issue 2, page e010541 ; ISSN 2051-1426 |
| Publisher Information: |
BMJ |
| Publication Year: |
2025 |
| Description: |
Background Antiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens collected from a randomized phase 2 trial of nivolumab with or without cabozantinib in 75 evaluable patients with recurrent endometrial cancer (NCI ETCTN 10104, NCT03367741 ). This trial demonstrated superiority of the combination to nivolumab alone. Methods and results Using Olink proteomics, mass cytometry, tumor antigen-specific ELISA, and whole exome tumor sequencing, we identified longitudinal immune signatures specific to cabozantinib use, including an increase in plasma HO-1 and reduction in plasma vascular endothelial growth factor receptor 2, interleukin-12, and circulating plasmacytoid dendritic cells. Prior exposure to immunotherapy and carcinosarcoma histology had no adverse impact on clinical benefit or biomarkers, and copy-number high tumors were associated with increased plasma granzymes on combination treatment. Higher baseline plasma levels of myeloid-related markers (chemokine ligand 23/CCL23, colony-stimulating factor-1/macrophage colony-stimulating factor/CSF1) were associated with poor overall and progression-free survival, and lack of clinical benefit (defined as progressive or stable disease |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1136/jitc-2024-010541 |
| Availability: |
https://doi.org/10.1136/jitc-2024-010541; https://syndication.highwire.org/content/doi/10.1136/jitc-2024-010541 |
| Rights: |
http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.AE35D49B |
| Database: |
BASE |