It is also important to note that the number of patients who tested positive for SARS-CoV-2 in this study excludes any patients who may have been infected but did not seek testing. “These databases are wonderful, but you only have data on patients who enter the database,” said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. “They didn’t look at all men with prostate cancer and ADT versus all men with prostate cancer not on ADT to see the incidence of infection,” Dr Rini pointed out.
Last month, in a collaboration with several other institutions, Vanderbilt launched the COVID-19 and Cancer Consortium (CCC19) to collect information on patients who have cancer, or a history of cancer, and who test positive for COVID-19. “It’s now over 100 institutions, and 2000 patients in the database,” said Dr Rini. The database will still miss any patients who may be infected with SARS-CoV-2 but never come in for testing, but it would include patients who test positive but do not require hospitalization.
The database captures information about demographics, cancer type, treatments, and so on. One of the projects using this data looks at how men with prostate cancer who are on ADT compare with other men in terms of the severity of the infection. “We can do internal matching to account for other variables that might be important, and see if this effect is observed in our dataset,” Dr Rini said.
Dr Bjartell is also planning a trial to test the effect of antiandrogen drugs on SARS-CoV-2 infection. The design of the study in Sweden will be that patients who test positive for the virus and are in a high-risk demographic, such as elderly people or those with cancer, will be randomly assigned to either standard of care or standard of care plus enzalutamide, a nonsteroidal antiandrogen medication. “We’re going to give the treatment for 5 days, and then we’re going to look at how many patients will need intensive care units,” he said. The study aims to enroll between 300 to 500 patients, both men and women, at several different centers in Sweden.
It’s possible that antiandrogen therapy could also help prevent the disease in women, Dr Bjartell said, but TMPRSS2 expression in women has not been well-characterized before now. Enzalutamide has been used to treat women with breast cancer, and is considered safe for women to take. “It would be very interesting to see if this hormone treatment works in both men and women,” he said.
Based on the results from Veneto, Dr Bjartell said, “there’s a very clear message that we should absolutely try to block this TMPRSS2 protein with androgen regulation.”
A clinical trial underway in the United States, led by Matthew B. Rettig, MD, of the University of California, Los Angeles, will test the efficacy of the hormone suppressor degarelix in reducing the COVID-19 severity. The phase 2 trial will be conducted at Veterans Affairs hospitals in Los Angeles, New York, and Seattle and will enroll 198 hospitalized male patients who have tested positive for the virus, but have not been intubated. Unlike the Swedish study, the VA trial will exclude women. “Estrogens may actually suppress TMPRSS2 expression, so degarelix would be predicted to worsen severity of the disease in women by lowering estrogen levels and thereby increasing TMPRSS2 expression,” wrote Dr Rettig in an email to Cancer Therapy Advisor.
- Montopoli M, Zumerle S, Vettor R, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (n=4532). Annals of Oncology. 2020;S0923-7534(20)39797-0.
- Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8.
- Baratchian M, McManus J, Berk M, et al. No evidence that androgen regulation of pulmonary TMPRSS2 explains sex-discordant COVID-19 outcomes [preprinted online April 21, 2020]. bioRxiv. doi: 10.1101/2020.04.21.051201
- Clinicaltrials.gov. Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH). NCT04397718. https://clinicaltrials.gov/ct2/show/NCT04397718. Accessed June 3, 2020.