COVID-19 Outcomes With Anticancer Drugs

The oncology community is engaged in ongoing research efforts to determine the effect of cancer and its treatment on the outcomes of patients who develop coronavirus 2019 disease (COVID-19) from SARS-CoV-2 infection. It is hypothesized that patients with cancer are at a greater risk of complications and/or death from COVID-19 because of immunosuppression or comorbidities associated with their malignancy or anticancer treatment. There is also an increased risk of exposure to the virus as a result of multiple health care encounters during their cancer care.

Understanding the potential COVID-19–related risks to patients with cancer is important because additional mitigation measures may be required — and it may help the cancer care team devise a treatment strategy that can minimize the patient’s risk of developing COVID-19 or experiencing complications associated with the virus.

Some early studies provide some information about these risks and include observational studies and registry data. However, it is important to note that sample sizes to date are small, and more studies are needed (and are currently under way) to more definitively determine the risk of active cancer and/or its treatment on the outcomes from COVID-19.

Active Cancer

A study of 218 patients with cancer in New York City found that patients with cancer were at a significantly higher risk of developing complications or dying from COVID-19 compared with matched controls who had COVID-19 but did not have cancer.¹ The authors cited that the general case fatality rate from New York City and the same health system ranged from 6% to 14%, whereas the case fatality rate for patients with solid tumors was 25% and 37% for hematologic malignancies. The case fatality rate increased with older age, but remained substantially higher among patients with cancer. In addition, comorbidities such as heart disease and chronic lung disease increased the risk of death.

Data from a cohort of 800 patients with cancer and symptomatic COVID-19 from the United Kingdom are consistent with the data from the New York City cohort, with a case fatality rate of 28%.² Risk of death with older age (odds ratio [OR], 9.42; 95% CI, 6.56-10.01; P <.0001) and presence of comorbidities, including hypertension (OR, 1.95; 95% CI, 1.36-2.80; P <.001) or other cardiovascular disease (OR, 2.32; 95% CI, 1.47-3.64; P =.002), were also elevated in this cohort. However, type of cancer and stage of cancer were not associated with the risk of death.

Another cohort in the United Kingdom of 35 patients with hematologic malignancy and COVID-19 demonstrated a case fatality rate of 40%, which increased with older age or the presence of comorbidities.³ An international cohort of 295 patients with lung cancer and COVID-19 found a case fatality rate of 49%.⁴

A cohort of 105 patients with cancer and COVID-19 from Wuhan, China, also found that patients with cancer were significantly more likely to die (OR, 2.34; 95% CI, 1.15-4.77; P =.03), be admitted to the intensive care unit (OR, 2.84; 95% CI, 1.59-5.08; P <.01), develop at least 1 critical symptom (OR, 2.79; 95% CI, 1.74-4.41; P <.01), or require mechanical ventilation compared with patients without cancer.⁵ Patients with metastatic cancer were at particularly higher risk of death (OR, 5.58; 95% CI, 1.71-18.23; P =.01). Another cohort from Hubei, China, demonstrated a case fatality rate of 20% among patients with cancer and severe COVID-19, as well as poorer prognosis among patients with a hematologic malignancy.⁶

A large cohort of 928 patients with cancer and severe COVID-19 from the United States, Canada, and Spain found a lower case fatality rate of 13%, which included 12% among patients with solid tumors or 14% among patients with hematologic tumors.⁷ However, patients with progressive cancer had a higher case fatality rate of 25%.

Active Anticancer Treatment

In the cohort of patients with cancer who were in New York City, active anticancer treatment with systemic or radiation therapy was not associated with an increased case fatality rate.¹ Similarly, a cohort of 800 patients with cancer and symptomatic COVID-19 from the United Kingdom found no effect of recent use of chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or radiotherapy on the risk of death from COVID-19 compared with patients who did not receive any of these therapies.² A cohort of 928 patients from the United States, Canada, and Spain also found no association between chemotherapy, non-chemotherapy medications, or radiotherapy and the risk of death from severe COVID-19.⁷

However, several other studies found that certain anticancer treatments may increase the risk of death from COVID-19. In the cohort from Hubei, patients who received chemotherapy (P =.002) or targeted therapy (P =.013) within 4 weeks before the onset of COVID-19 symptoms had a higher risk of death compared with patients who did not.⁶ There was no association between surgery or radiotherapy and the risk of death, but the sample sizes were very small.

In an international cohort of 295 patients with lung cancer and COVID-19, recent use of chemotherapy alone or in combination with another agent (HR, 1.71; 95% CI, 1.12-2.63; P =.025) was significantly associated with an increased risk of death from COVID-19 compared with patients who received no recent anticancer therapy.⁴ The association was likely due to chemotherapy, as use of other anticancer therapies alone or in combination were not associated with an increased risk of death.

Across all studies that included it, immune checkpoint inhibitor (ICI) monotherapy was not associated with an increased risk of serious COVID-19 or death, but the number of patients taking these agents was also small.^1,6

Steroid Treatment

Corticosteroids may be used to treat severe COVID-19, and some patients with cancer may already be receiving corticosteroids as part of their cancer care. Results from studies of corticosteroid treatment of COVID-19 among patients without cancer are mixed, with some showing a survival benefit and others showing no benefit.⁸ However, there are few studies that have evaluated the effect of corticosteroid use among patients with cancer and COVID-19.

In a cohort of 295 patients with lung cancer and COVID-19, steroid use before COVID-19 diagnosis “trended toward” an association with an increased risk of death from COVID-19 (HR, 1.49; 95% CI, 1.00-2.23; P =.052).⁴ In the Hubei cohort, the use of intravenous corticosteroids to treat COVID-19 among patients with cancer occurred more frequently among patients who died compared with those who survived (P <.0001); however, it is unclear whether this is an independent association.⁶

Conclusions

The current evidence suggests that patients with cancer, particularly those with hematologic malignancies or lung cancer, are likely at increased risk of severe COVID-19 and death from COVID-19 compared with patients without cancer. The reason for this is not clear, but the risk of death increases with older age and the presence of certain comorbidities, both of which are common among patients with cancer.

Most data suggest that anticancer therapies do not have an effect of COVID-19 outcomes, although several studies suggest that recent chemotherapy administration may increase the risk of death. Importantly, studies that have evaluated the role of anticancer therapy generally have small sample sizes, and more data are needed to come to a definitive conclusion about how cancer therapies could impact outcomes from COVID-19.

There are few data that evaluate steroid use, either as part of cancer care or to treat COVID-19, among patients with cancer, but some studies suggest that steroid use may increase the risk of death. However, in both of the mentioned studies, the patient sample size was small, which limits the ability for researchers to draw conclusions.

References

1. Mehta V, Goel S, Kabarriti R, et al. Case fatality rate of cancer patients with COVID-19 in a New York hospital system [published online May 1, 2020]. Cancer Discov. doi: 10.1158/2159-8290.CD-20-0516
2. 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 [published online May 28, 2020]. Lancet. doi: 10.1016/S0140-6736(20)31173-9
3. Aries JA, Davies JK, Auer RL, et al. Clinical outcome of coronavirus disease 2019 in haemato-oncology patients [published online May 18, 2020]. Br J Haematol.
4. Horn L, Shisenant JG, Torri V, et al. Thoracic Cancers International COVID-19 Collaboration (TERAVOLT): Impact of type of cancer therapy and COVID therapy on survival. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr LBA111. 
5. Dai M, Liu D, Liu M, et al. Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak [published online April 28]. Clin Cancer Res. doi: 10.1158/2159-8290.CD-20-0422
6. Yang K, Sheng Y, Huang C, et al. Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study [published online May 29, 2020]. Lancet Oncol.
7. Kuderer NM, Choueiri TK, Shah DP, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study [published May 28, 2020]. Lancet. doi: 10.1016/S0140-6736(20)31187-9
8. Veronese N, Demurtas J, Yang L, et al. Use of corticosteroids in coronavirus disease 2019 pneumonia: a systematic review of the literature. Front Med(Lausanne). 2020:7:170. doi: 10.3389/fme