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Two Cohort Studies Identify Risk Factors for Mortality in Patients With Cancer and COVID-19


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Two studies recently reported in The Lancet have identified risk factors for mortality among patients with cancer and COVID-19.1,2

As reported by Lennard Y.W. Lee, DPhil, of the Institute of Cancer and Genomic Sciences, University of Birmingham, and colleagues,1 a UK prospective cohort study performed by the UK Coronavirus Cancer Monitoring Project (UKCCMP) has found that an increased risk of COVID-19 mortality is associated with such factors as increased age, male sex, and comorbidities but not with recent use of cancer chemotherapy or other treatments.

Lennard Y.W. Lee, DPhil

Lennard Y.W. Lee, DPhil

Nicole M. Kuderer, MD

Nicole M. Kuderer, MD

As reported by Nicole M. Kuderer, MD, of the Advanced Cancer Research Group, Kirkland, Washington, and colleagues,2 a cohort study using the COVID-19 and Cancer Consortium (CCC19) database has shown that an increased risk of 30-day all-cause mortality in patients with COVID-19 and cancer is also associated with increased age, male sex, and number of comorbidities, as well as active cancer, but not with such factors as cancer type, recent anticancer therapy, or recent surgery.

UKCCMP Study Details

The UKCCMP was launched on March 18, 2020.1 All patients with cancer presenting to 55 cancer centers in the United Kingdom national network from March 18 to April 26, 2020, with COVID-19 were eligible for enrollment. To be included in analysis, patients had to have laboratory-confirmed symptomatic COVID-19 infection.

The first 800 eligible patients enrolled were included in the study. Among all patients, the median age was 69 years, and 56% were male. The most common cancer types were those of digestive organs (19%), breast cancer (13%), and hematologic malignancies, including lymphoma in 8%. A total of 34% of patients had received no cancer treatments within 4 weeks prior to diagnosis of COVID-19 infection. Cancer treatments received by patients within 4 weeks of COVID-19 diagnosis included chemotherapy in 35%, radiotherapy in 10%, targeted treatment in 9%, hormone therapy in 8%, immunotherapy in 6%, and surgery in 4%.

UKCCMP: Mortality Risk Factors

Among the 800 patients, 412 (52%) had a mild COVID-19 course, and 226 (28%) patients died. On univariate analysis, the risk of death was significantly associated with increased age (odds ratio [OR] = 9.42, P < .0001; median age of nonsurvivors vs survivors = 73 vs 66 years), male sex (OR = 1.67, P = .003), presence of hypertension (OR = 1.95, P < .001), and presence of cardiovascular disease (OR = 2.32, P < .001). Significant associations were also observed for severe and critical COVID-19 severity scores and treatment in intensive therapy units. No significant association was observed for cancer types or stages or cancer treatments within 4 weeks of a COVID-19 diagnosis.

KEY POINTS

  • Based on the findings of two cohort studies, risk factors for mortality in patients with cancer and COVID-19 included increased age, male sex, and comorbidities.
  • Receipt of cancer treatment within 4 weeks of a COVID-19 diagnosis was not found to be associated with an increased risk of mortality.

On multivariate analysis adjusting for age, sex, and comorbidities, no significant association with mortality was found for receipt vs no receipt of chemotherapy in the past 4 weeks (OR = 1.18, P = .380), with no significant effect also being observed for radiotherapy vs no radiotherapy (OR = 0.65, P = .159), targeted therapy vs no targeted therapy (OR = 0.83, P = .559), hormone therapy vs no hormone therapy (OR = 0.90, P = .744), or immunotherapy vs no immunotherapy (OR = 0.59, P = .177).

In further multivariate analysis (adjusted for age, gender, and comorbidities) including patients who had received chemotherapy within 4 weeks of a COVID-19 diagnosis, a significantly reduced risk of death was associated with nonpalliative vs palliative chemotherapy (16% vs 35%; OR = 0.40, P = .040). No significant effect was observed for palliative first-line chemotherapy vs other line (OR = 0.84, P = .690), palliative chemotherapy vs no chemotherapy (OR = 1.48, P = .102), or palliative chemotherapy vs no cancer treatment (OR = 1.05, P = .854).

The investigators concluded: “Mortality from COVID-19 in patients with cancer appears to be principally driven by age, gender, and comorbidities. We are not able to identify evidence that patients with cancer on cytotoxic chemotherapy or other anticancer treatment are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment.”

“Mortality from COVID-19 in patients with cancer appears to be principally driven by age, gender, and comorbidities."
— Lennard Y.W. Lee, DPhil

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CCC19 Study Details

The CCC19 was formed on March 15, 2020, to study the characteristics and course of illness among patients with COVID-19 with a current or past diagnosis of cancer.2 Accrual to the registry began on March 17, 2020. The registry is an electronic REDCap database maintained at Vanderbilt University Medical Center, Nashville. Participating institutions have been restricted to the United States and Canada. Participation of anonymous individual health-care practitioners in Argentina, Canada, the European Union, United Kingdom, and United States is permitted.

The study focused on data from 928 patients with active or a previous malignancy, aged  18 years or older, with laboratory-confirmed COVID-19 infection from the United States, Canada, and Spain, with information entered into the database between March 17 and April 16, 2020, and follow-up data through May 7, 2020 (date of analysis). The primary endpoint was all-cause mortality within 30 days of a COVID-19 diagnosis. In multivariate analyses, odds ratios for age, sex, smoking status, and obesity were each adjusted for the other factors; other covariates were adjusted for age, sex, smoking status, and obesity.

Among the 928 patients, the median age was 66 years, with 30% aged 75 years or older, and 468 (50%) were male. The most common malignancies were breast (21%) and prostate (16%) cancers. Overall, 39% of patients were on active cancer treatment, and 43% had active (measurable) cancer. A total of 811 patients (87%) were from the United States (Northeast = 40%; Midwest = 22%; South = 13%; and West = 13%), 68 (7%) were from Spain, and 49 (5%) were from Canada. A total of 60% of patients had received no anticancer treatment within 4 weeks prior to a COVID-19 diagnosis, 22% had received noncytotoxic therapy (including targeted therapy in 8%, endocrine therapy in 9%, immunotherapy in 4%, radiotherapy in 1%, and cancer-related surgery in less than 1%), and 17% had received cytotoxic systemic therapy; 3% had any surgery within 4 weeks of a COVID-19 diagnosis.

CCC19: Mortality Risk Factors

At the time of analysis, 121 patients (13%) had died. On multivariate analysis, factors independently associated with an increased risk of 30-day mortality were increased age (OR per 10-year increase = 1.84, 95% confidence interval [CI] = 1.53–2.21), male sex (OR = 1.63, 95% CI = 1.07–2.48), smoking status of former vs never (OR = 1.60, 95% CI = 1.03–2.47), at least 2 vs 0 comorbidities (eg, OR for 2 vs 0 = 4.50, 95% CI = 1.33–15.28), Eastern Cooperative Oncology Group performance status of at least 2 (eg, OR for 2 vs 0 = 3.89, 95% CI = 2.11–7.18), active cancer (compared with remission/no evidence of disease: OR for present, stable, or responding to treatment = 1.79, 95% CI = 1.09–2.95); OR for present, progressive disease = 5.20, 95% CI = 2.77–9.77), and residence in the U.S. Northeast (reference category) vs Canada (OR = 0.24, 95% CI = 0.07–0.84) or U.S. Midwest (OR = 0.50, 95% CI = 0.28–0.90).

Receipt of azithromycin plus hydroxychloroquine vs neither was also associated with an increased risk of mortality (OR = 2.93, 95% CI = 1.79–4.79); however, the finding may be confounded by the use of the combination primarily in patients with more severe COVID-19 infection.

No significant associations were observed for race/ethnicity, obesity, cancer type (hematologic malignancy or multiple cancers vs solid tumors), type of anticancer therapy vs no therapy within 4 weeks prior to a COVID-19 diagnosis, or surgery vs no surgery within 4 weeks of a COVID-19 diagnosis.

Compared with no receipt of treatment within the 4 weeks prior to a COVID-19 diagnosis, odds ratios for treatment within the prior 4 weeks were 1.04 (95% CI = 0.62–1.76) for noncytotoxic therapy, 1.47 (95% CI = 0.84–2.56) for cytotoxic systemic therapy, and 1.52 (95% CI = 0.58–3.96) for any surgery.

"Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.”
— Nicole M. Kuderer, MD

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The investigators concluded: “Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.” 

DISCLOSURE: The UKCCMP study was funded by the University of Birmingham and the University of Oxford. The CCC19 study was funded by the American Cancer Society, the National Institutes of Health, and the Hope Foundation for Cancer Research. For full disclosures of both study authors, visit thelancet.com.

REFERENCES

1. Lee LYW, Cazier JB, Starkey T, et al: COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: A prospective cohort study. Lancet 395:1919-1926, 2020.

2. Kuderer NM, Chouieri TK, Shah DP, et al: Clinical impact of COVID-19 on patients with cancer (CCC19): A cohort study. Lancet 395:1907-1918, 2020.


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