Faculty, Staff and Student Publications
Publication Date
12-5-2024
Journal
Nature Communications
Abstract
Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We performed comprehensive molecular, immune, microbiome, and metabolic profiling on samples of trial patients. Here, we show increased T and B cell clusters and distinct microbial patterns with amino acid and lipid metabolism are linked to exceptional clinical responses. This study suggests the immune milieu and host-microbiome can be leveraged to improve antitumor response in future immunotherapy trials.
Keywords
Humans, Female, Ovarian Neoplasms, Immunotherapy, Gastrointestinal Microbiome, Bevacizumab, Middle Aged, Antibodies, Monoclonal, Humanized, Aged, Cyclophosphamide, Progression-Free Survival, Adult, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Recurrence, Local, Quality of Life, Treatment Outcome, Multiomics
DOI
10.1038/s41467-024-54565-8
PMID
39638782
PMCID
PMC11621351
PubMedCentral® Posted Date
12-5-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons