Patients with cancer who received ACE2-lowering antineoplastic compounds had a significantly lower rate of SARS-CoV-2 infection compared with patients who received other antineoplastic drugs, according to a study published in JAMA Oncology.
“The ACE2-lowering compounds may alter SARS-CoV-2 activity through ACE2 downregulation and/or other plausible antiviral mechanisms,” the researchers wrote.
The researchers identified the ACE2-lowering compounds using the Library of Integrated Network-Based Cellular Signatures database. In silico analysis of gene expression signatures after treatment revealed 91 antineoplastic compounds that were associated with downregulation of ACE2 across cell lines.
The researchers then retrospectively evaluated 1701 cancer patients undergoing antineoplastic therapy at a single center from March 10, 2020, through May 28, 2020, to see if treatment with ACE2-lowering antineoplastics lowered the risk of SARS-CoV-2 infection.
Of the 1701 patients evaluated, 1553 had solid tumors, 394 had hematologic malignancies, and 312 patients had more than 1 cancer type.
There were 215 patients (12.6%) who received treatment with any of 8 ACE2-lowering antineoplastic compounds. The 8 compounds included mTOR/PI3K inhibitors (everolimus, temsirolimus, and alpelisib), antimetabolites (decitabine and gemcitabine), a mitotic inhibitor (cabazitaxel), and other kinase inhibitors (dasatinib and crizotinib).
Patients who received these ACE2-lowering compounds were significantly less likely to have a positive SARS-CoV-2 test compared with patients who received other antineoplastic therapies — 7.0% and 12.9%, respectively. In a multivariable analysis, the odds ratio (OR) was 0.53 (95% CI, 0.29-0.88; P =.02).
When the researchers evaluated all 8 ACE2-lowering drugs together in a univariable analysis, the drugs were associated with a significant reduction in the risk of SARS-CoV-2 infection (OR, 0.51; P =.01). However, when the researchers looked at the drugs individually, only gemcitabine was significantly associated with a decreased risk of SARS-CoV-2 (OR, 0.42; P =.01). The researchers did note that the individual drug analyses were “likely underpowered.”
“Examination of each study drug shows that the majority of associated ACE2-lowering antineoplastics (6 of 8) were associated with at least an absolute 3% reduction in SARS-CoV-2 positivity,” the researchers wrote.
The team also found that ACE2-lowering antineoplastics were not significantly associated with hospital admission, hypoxic event, or death.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Foote MB, White JR, Jee J, et al. Association of antineoplastic therapy with decreased SARS-CoV-2 infection rates in patients with cancer. JAMA Oncol. Published online August 19, 2021. doi:10.1001/jmaoncol.2021.3585