SITC 2020: Cyclophosphamide Prior to Pembrolizumab in Metastatic Triple-Negative Breast Cancer
Posted: Wednesday, November 25, 2020
Mark Woodcock, MD, of Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, and colleagues conducted a clinical trial to test whether a single, priming dose of cyclophosphamide prior to pembrolizumab would improve progression-free survival in patients with metastatic triple-negative breast cancer. It is known that progression-free survival with chemotherapy alone takes about 2 to 4 months, but recovery with single-agent checkpoint inhibitors is restricted by modest response rates. The results of this study were presented at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 258) and published in the Journal for ImmunoTherapy of Cancer.
“Response to checkpoint inhibitor therapy was associated with immunogenomic features of programmed cell death and B-cell activation. Pretreatment circulating immunoglobulin diversity measures also correlated with future response to therapy,” stated the researchers. “Taken together, these data suggest that B-cell activity contributes significantly to response to checkpoint inhibitor therapy in metastatic triple-negative breast cancer.”
A total of 40 patients with pretreated metastatic triple-negative breast cancer were enrolled. Tumor samples were collected before enrollment, and peripheral blood mononuclear cell specimens were taken before cyclophosphamide treatment, as well as prior to each pembrolizumab cycle. Tumor RNA sequencing was performed for 31 patients, and about 15 had matched peripheral blood mononuclear cell–derived immune chains before and after treatment. Tumor samples collected from lymph nodes were excluded from the trial when preliminary RNA-sequencing samples showed upregulation in B-cell receptor pathways.
Response to therapy (16%) was correlated to tumor RNA sequencing, with gene pathways involving apoptosis and MAPK activation. Tumors that did not respond were enriched in G-protein signaling and inhibition of insulin secretion. Immune gene signatures corresponding to B-cell activation and natural killer cells, signaling, and interaction with T follicular helper cells were indicative of response. There was a noteworthy association between richness and peripheral immunoglobulin high-chain abundance.
Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.