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Certain cancer drugs that lower levels of angiotensin-converting enzyme 2 (ACE2) may offer some protection against infection with SARS-CoV-2, suggests a new study.
Those drugs include TOR/PI3K inhibitors (everolimus, temsirolimus, and alpelisib), antimetabolites (decitabine and gemcitabine), mitotic inhibitors (cabazitaxel), and other kinase inhibitors (dasatinib and crizotinib).
The study, which was conducted at the Memorial Sloane Kettering Center (MSKCC), New York City, involved 1701 patients who underwent treatment for cancer during the early months of the COVID-19 pandemic, from March 10 through May 28, 2020.
The investigators found that among patients who were treated with cancer drugs that lower ACE2 levels, there was a significantly lower rate of positive SARS-CoV-2 tests than among patients who were taking other drugs (7% vs 12.9%).
Study author Michael Foote, MD, a research fellow at MSKCC, said the study has several implications. “Many oncologists worry that treating patients with certain cancer drugs may lead to an increased risk of COVID-19,” he told Medscape Medical News. “Because of this paper, some oncologists may feel a little more comfortable treating a patient with a certain drug from our list during the pandemic.”
In addition, he suggested the findings may spur new research. “There is a great deal of interest in the discovery of new molecular signaling patterns that the virus uses to survive and replicate,” he said. This finding of a possible decrease in viral infectivity suggests that these particular compounds may impair specific signaling pathways that SARS-CoV-2 needs to replicate. “Further research studies can explore these new viral signaling pathways in a lab to better understand how the virus replicates and also potentially design new antiviral drugs for all patients, not just cancer patients,” Foote commented.
The study was published online August 19 in JAMA Oncology.
Cancer Patients at Risk
The authors note that engineered anti-ACE2 therapies have shown preliminary success as COVID-19 treatments and that computer modeling and in vitro analysis have predicted that the use of repurposed antineoplastic agents that inhibit proliferative signaling pathways hijacked by SARS-CoV-2 may inhibit the activity of the virus.
For the first part of their study, the team used computer simulation to identify cancer drugs that were associated with decreased ACE2 gene expression. They then evaluated how patients who were taking these drugs fared during the pandemic.
From 1701 study participants, 215 (12.6%) patients received an ACE2-lowering antineoplastic drug.
After adjusting for confounders, among patients who received an ACE2-lowering cancer drug, the SARS-CoV-2 positivity rate was statistically significantly lower at 7.0% (15 of 215 patients) vs 12.9% (191 of 1486 patients) among those who received other therapies.
In particular, the use of gemcitabine was associated with a decrease in SARS-CoV-2 positivity (odds ratio [OR], 0.42).
Use of ACE2-lowering cancer drugs was not statistically significantly associated with hospital admission, hypoxic event, or death among all patients or in the SARS-CoV-2-positive-only subcohort.
The rate of SARS-CoV-2 infections was increased among non-White or Hispanic patients in comparisoin with White non-Hispanic patients (OR, 1.78).
Most of the patients in this study (91.3%) had solid tumors; 23.2% of patients had a hematologic cancer; and 18.3% patients had more than one type of cancer.
Foote emphasized that the study is a retrospective analysis, not a randomized controlled trial (RTC). RTCs are the gold standard for determining whether a drug works for a patient, he commented.
In addition, these findings come from very early in the pandemic, before COVID-19 vaccines were available. “In some ways, this may be a strength of the study, as we assessed the effect of certain drugs on the virus pre-vaccine, so we glimpsed a snapshot of the innate behavior of SARS-CoV-2,” Foote said.
However, it is unclear how to apply these findings now that effective vaccines are available. “Certainly we know that vaccines are the most effective ways to prevent viral spread,” he added. “The Delta variant has been shown to have an especially high attraction between the virus and the ACE2 receptor; it is unknown if our drugs would be more or less effective against this variant.”
The study was supported by several research grants, including grants from Stand Up to Cancer and the National Institutes of Health. Foote has disclosed no relevant financial relationships. Several co-authors have disclosed relationships with industry, as listed in the original article.
JAMA Oncol. Published Online August 19, 2021. Full text
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