Active Cancer Strongly Associated With Increased COVID-19 Mortality

Jeremy L. Warner, MD, MS, an associate professor of medicine at Vanderbilt University Medical Center

Jeremy L. Warner, MD, MS

An analysis of data collected in the COVID-19 and Cancer Consortium (CCC19) registry showed that patients with progressive cancer were 5.2-times more likely to die within 30 days of being diagnosed with novel coronavirus 19 (COVID-19) compared with patients in remission or with no evidence of disease.^1,2

The risk for death was 1.79 times greater for those with stable cancer compared with patients who had no evidence of disease.

Lead author Jeremy L. Warner, MD, and his colleagues assessed data on 928 patients for 30-day all-cause mortality. At a median follow-up of 21 days, 121 (13%) patients in the study had died of COVID-19. "That's about twice what the [death rate] is for all patients across the globe, which is about 6.5%," he said.

As of May 28, the World Health Organization had recorded more than 5.5 million cases of COVID-19 and more than 351,000 deaths.³ According to the Centers for Disease Control and Prevention, 12% of US deaths for the week ending May 16 were attributed to pneumonia, influenza, or COVID-19.⁴

Warner, associate professor of medicine and biomedical informatics at Vanderbilt University Medical Center in Nashville, Tennessee, presented the results during a press briefing in advance of the 2020 ASCO Virtual Scientific Program. The data were also published in The Lancet.

Warner said that treating COVID-19 with a combination of hydroxychloroquine and azithromycin, a regimen that has been promoted by President Donald Trump, was associated with a 2.89-fold greater risk of 30-day mortality compared with patients who did not receive either drug.

"I will add that this final result is of uncertain validity due to a high risk of residual confounding," Warner added. "For example, patients receiving this combination were more likely to have severe disease or more likely to be hospitalized."

Patients who later died after receiving hydroxychloroquine and azithromycin were more likely to have had slightly diminished daily physical function, received cancer therapy less than 2 weeks before COVID-19 diagnosis, have Rh-positive blood type, be of non-Hispanic ethnicity, and use statins at baseline.

Investigators did not observe an increased risk for death associated with the use of either drug as monotherapy.

On May 22, The Lancet published results online from an observational study of 96,032 patients hospitalized with COVID-19 at 671 hospitals worldwide. Mehra et al found that hydroxychloroquine was associated with an increased risk for in-hospital mortality (18.0%; HR, 1.335; 95% CI, 1.223-1.457) and de-novo ventricular arrhythmia during hospitalization (6.1%; HR, 2.369; 95% CI, 1.935-2.900) compared with patients who did not receive the antimalaria drug.⁵

CCC19 includes 108 organizations in 43 states that collect and share data about patients with cancer who have been diagnosed with COVID-19. The consortium aims to collect and disseminate prospective, granular, uniformly organized information on these patients as broadly and as rapidly as possible.

Overall, 43% of patients included in the study had active cancer, 39% were on active cancer treatment, and 45% were in remission. The most common cancer was breast (21%), followed by prostate (16%), gastrointestinal (12%), lymphoma (11%), and thoracic (10%).

Half of patients in the registry were men and half were white. African Americans and Hispanics each made up 16% of the cohort, with other races and ethnicities making up 15%. The median age was 66 years and 30% of patients were aged 75 years or older.

More than half (52%) of patients were never smokers, 37% were former smokers, 5% were current smokers. Sixty-eight percent had ECOG status of 0 or 1 and 13% had an ECOG status of 2 or higher. ECOG status was unknown for 19% of patients.

ECOG status of 2 or higher (35%), active cancer (25%), age older than 75 (25%), former smoker (20%), and male sex (17%), were all independent risk factors for COVID-19 mortality. Compared with patients with an ECOG score of 1 or lower, those with a score of 2 or higher had a 3.89 times greater risk for 30-day mortality. The risk for 30-day mortality was 1.6 times greater for smokers compared with nonsmokers and 1.63 times greater for men compared with women. Each additional decade of life was associated with a 1.83-fold increased risk for death.

"The only characteristic we found that was associated with a lower rate of mortality was not having comorbidities, although the number of deaths in that group was small and does not reach statistical significance," Warner added. Three (2%) patients in that subgroup died during the study.

Investigators did not find any statistically significant rates of death based on race or ethnicity.

"The cancer care community urgently needs data on the effects of COVID-19, specifically in patients with cancer," ASCO President Howard A. Burris III, MD, stated in a news release. "How we improve the care we provide these patients and reduce the number of deaths and severe consequences associated with this disease are among the top questions. The COVID-19 and Cancer Consortium registry is a great example of the community quickly coming together to identify and collect the data we need on a large scale."

References

1. Warner JL, Rubinstein S, Grivas P, et al. Clinical impact of COVID-19 on patients with cancer: Data from the COVID-19 and Cancer Consortium (CCC19). 2020 ASCO Virtual Scientific Program. Abstract LBA110.
2. Kuderer NM, Choueiri TK, Shah DP, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Accessed May 28, 2020. doi:10.1016/S0140-6736(20)31187-9
3. World Health Organization. Coronavirus disease (COVID-19) dashboard. Accessed May 28, 2020. https://covid19.who.int/
4. Centers for Disease Control and Prevention. COVIDView. Accessed May 28, 2020. https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html
5. Mehra MR, Desai SS, Ruschitzka F, et al. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Accessed May 28, 2020. doi:10.1016/S0140-6736(20)31180-6

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