medwireNews: Early research points to the potential activity of certain anticancer drugs against SARS-CoV-2.
“Antineoplastic compounds that target cellular machinery used by SARS-CoV-2 for entry and replication, including angiotensin-converting enzyme 2 (ACE2), may disrupt SARS-CoV-2 activity,” explain Luis Diaz Jr (Memorial Sloan Kettering Cancer Center, New York, USA) and co-researchers in JAMA Oncology.
They therefore used the Library of Integrated Network-Based Cellular Signatures (LINCS) database to identify 91 anticancer drugs “associated with considerably reduced ACE2 gene expression across cell lines,” of which eight had been used in a cohort of 1701 patients with a diverse range of tumors who underwent SARS-CoV-2 PCR testing at Memorial Sloan Kettering Cancer Center between March 10 and May 28, 2020.
The compounds in question were the mTOR/PI3K inhibitors everolimus, temsirolimus, and alpelisib, the antimetabolites gemcitabine and decitabine, the mitotic inhibitor cabazitaxel, and the kinase inhibitors crizotinib and dasatinib.
Just over half (55.8%) of the patients were women, and the majority (91.3%) had a solid tumor, while 23.3% had a hematologic malignancy and 18.3% had more than one cancer type.
The incidence of SARS-CoV-2 infection was significantly lower among the 12.6% of participants who received a potential ACE2-lowering antineoplastic drug than the remaining 87.4% who did not, at rates of 7.0% and 12.9%, respectively, and an odds ratio (OR) of 0.53 after adjustment for confounders in a multivariable analysis.
“This association was consistent in sensitivity analyses that used different LINCS data set significance thresholds to select ACE2-lowering antineoplastics,” and in multivariable analyses that adjusted for specific cancer types or steroid use, as well as in a propensity score-matched subcohort, say Diaz and colleagues.
They add, however, that there was no statistically significant association between the use of ACE2-lowering agents and reduced rates of hospitalization, hypoxic events, or death in either the full cohort or the SARS-CoV-2-positive subgroup, “potentially because of low numbers of observed events.”
Analysis by individual drug showed that all but two of the eight drugs, namely cabazitaxel and alpelisib, were associated with an absolute decrease in SARS-CoV-2 positivity of at least 3%, with a significant association between gemcitabine use and a reduced incidence of SARS-CoV-2 infection (univariable OR=0.42). The SARS-CoV-2 positivity rates in patients who did versus did not use gemcitabine were 5.8% and 12.9%, respectively.
Discussing the limitations of the study, the researchers note that it was “difficult to assess” mortality from active cancer versus COVID-19, and they add: “Potential protective effects from ACE2-lowering antineoplastics must also be taken in the context of additional immune protection advances that occurred poststudy, including vaccination.”
Nonetheless, the team believes that “[t]he study is hypothesis generating and serves to direct further experimental exploration of the molecular mechanisms underlying anti–SARS-CoV-2 activity for potential ACE2-lowering antineoplastic agents.”
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JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.3585