Treatment and Outcomes Data Are Evolving for Patients With COVID-19 and Cancer

New evidence is evolving every day on clinical outcomes and different treatment options for patients with underlying medical conditions who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the coronavirus disease 2019 (COVID-19).¹ Currently, there is conflicting primary literature on whether adult patients with a diagnosis of active cancer are at an increased risk of developing severe illness from SARS-CoV-2 infection, and the correlation of the concomitant disease states, as well as treatment, is not well understood.^1,2

According to the CDC, having cancer increases your risk of severe illness from COVID-19.^1,2 Severe illness from SARS-CoV-2 infection is defined as hospitalization, admission to the intensive care unit (ICU), intubation or mechanical ventilation, and death.¹ Owing to this conflicting evidence, a comprehensive systematic search of 12 cohort study results that assessed cancer comorbidity and risk of mechanical ventilation or death in patients with confirmed COVID-19 found that patients had a lower risk of mechanical ventilation and death than patients without cancer.³ However, the authors felt that because of limited numbers, larger studies that include various malignancies from different centers are needed. In contrast, in a large systematic meta-analysis encompassing 110 studies from 10 countries analyzed pooled in-hospital mortality risk of COVID-19 in patients with cancer, results showed the estimated risk was between 9% and 20% across all settings.⁴

Among 904 patients hospitalized, the pooled mortality risk estimate of 14.1% was at least 5 times higher than the reported mortality risk of COVID-19 in nonelderly patients without underlying predisposing conditions across Europe and North America, which was 0.7% to 2.6%.4 Although there is conflicting primary literature, the CDC’s recent update should caution health care providers to take a closer look at this patient population.

It is reasonable to presume that patients with concomitant cancer and COVID-19 are at a higher risk of complications because of the systemic immunosuppressive state caused by cancer and the therapy used to treat it.^5,6 Results from a small, retrospective study performed in China evaluated 18 patients with cancer and a diagnosis of SARS-CoV-2 infection found that patients had 3.5 times the risk of requiring mechanical ventilation or ICU admission, compared with the general population without cancer.⁵ Though the study results showed that patients with cancer are at an increased risk of complications, the small sample size of patients prevented the investigation of specific cancer-associated risk factors for worse outcomes.⁵

A much larger retrospective case-control study comprising 73.4 million patient electronic health records from 360 hospitals across the United States aimed to assess the risk of contracting COVID-19 among 13 common cancer types and the risks associated with adverse outcomes.⁷ Of the millions of records analyzed, 1200 patients had cancer and received a diagnosis with COVID-19 within 1 year of the study end-date, August 12, 2020. Overall, patients with cancer and COVID-19 had significantly worse outcomes (hospitalization, 47.46%; death, 14.93%) than patients with COVID-19 without cancer (hospitalization, 24.26%; death, 5.26%) (P < .001).⁷ They concluded that there was a synergistic effect between COVID-19 and cancer on death and hospitalization rates, but the underlying biological mechanisms for this synergy warrants further investigation.⁷

Because the risk of developing severe illness from COVID-19 in patients with different types of cancer is not fully characterized, clinicians are attempting to dig deeper to find nuanced correlations.6 In a large cohort study performed across 14 hospitals in Hubei Province, China, from January 1, 2020, to February 24, 2020, 105 patients with cancer and 536 age-matched patients without cancer with confirmed COVID-19 were assessed for clinical characteristics and outcomes.⁸ Investigators found that the patients with cancer were more likely to have severe outcomes than the patients without cancer, largely due to the types of tumors. The findings suggested that lung cancer, metastatic disease, and hematologic malignancies may be associated with higher rates of COVID-19-related ICU admissions and mortality.⁸

In terms of cancer therapy, different types of treatments such as immunotherapy, chemotherapy, targeted therapy, and surgery had independent influences on the severity of illness and mortality associated with COVID-19. In the study, patients receiving immunotherapy had the highest severity of illness and death rate. However, because of the wide range of treatments utilized in patients and the small number of patients receiving immunotherapy, conclusions were difficult to draw; therefore, a larger case population is warranted to understand this relationship better.⁸

To further evaluate the effects of immunotherapy as cancer treatment, a multicenter, retrospective analysis of 113 patients with cancer and laboratory-confirmed COVID-19 across North America, Europe, and Australia aimed to shed light on the effects on mortality.⁹ Immunotherapy, or immune checkpoint inhibitors (ICIs), use substances to stimulate or suppress the immune system.¹⁰ In this study, ICIs utilized were PD-1 or PD-L1 inhibitors or a combination of PD-1 or PD-L1 plus a CTLA-4 inhibitor.⁷ A large percentage of the patient population was from Europe (64%), and about one-third (33%) were from North America. Symptoms, comorbidities, and medications, in addition to investigations and treatments implemented for COVID-19, were analyzed. Investigators sought to look at hospital and ICU admissions and mortalities. Overall, results showed that for hospital and ICU admission, 61% of patients were discharged, 12% stayed in the hospital, and 27% of those admitted died by the data cutoff of May 15, 2020. The analysis results concluded that 9 patients died and this was not attributed to treatment with immunotherapy. Overall, they concluded that patients who received immunotherapy within 12 months of testing positive for COVID-19 did not increase the risk of mortality in patients.⁹

Considering patients with cancer and concomitant SARS-CoV-2 infection are more vulnerable to severe outcomes, managing their cancer therapy during the pandemic can be challenging for clinicians.¹¹ Many patients with cancer may need aggressive treatment due to the nature of their underlying disease; however, the clinical effects of cancer therapy in conjunction with COVID-19 are not fully known, and what data are available provide conflicting results.⁶ A study performed at a hospital in New York City from March 2020 to April 2020 assessed clinical characteristics and outcomes from 309 patients with cancer who received cytotoxic chemotherapy within 35 days of a COVID-19 diagnosis.⁶ Results showed that receipt of cytotoxic chemotherapy was not associated with adverse COVID-19 outcomes.⁶ Further adding to these data, 2 large observational studies were performed in patients with cancer and a confirmed SARS-CoV-2 infection between March 2020 and April 2020. Results of this study found the primary end point of all-cause mortality was not increased due to recent cytotoxic chemotherapy or other anticancer treatment.^12,13

On the other hand, results from a study conducted in China of 205 patients with cancer and COVID-19 showed that receiving cytotoxic chemotherapy 4 weeks before symptom onset had a higher mortality rate.¹⁴ Study results also found that patients with hematological malignancies had a poorer prognosis than those with solid tumors. The authors concluded that the evidence might not strongly prove that the patients studied have a higher fatality rate than the general patient population, and clinicians should be cautious when deciding whether or not to use cytotoxic chemotherapy in these patients.¹⁴ Overall, it is challenging to compare these studies because they vary in their end points and their statistical methods.^6,12-14

In a prospective observational study of 928 patients across the United States, Canada, and Spain from the COVID-19 and Cancer Consortium database, authors expressed that these data strongly indicate that COVID-19 mortality in patients with cancer is mainly driven by advancing age and the presence of other noncancer comorbidities.¹² As a result, they do not suggest that chemotherapy or anticancer treatments will necessarily increase the risk of mortality from COVID-19.¹² Adding to these data, prospective observational study results in 800 patients with active cancer in the UK Coronavirus Cancer Monitoring Project (UKCCMP) found that mortality from COVID-19 in patients with cancer appears to be mainly driven by age, gender, and comorbidities.¹³ The study results could not 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. The UKCCMP is the first COVID-19 clinical registry that enables near real-time reports to frontline doctors about the effects of COVID-19 on patients with cancer, so these data are promising.¹³

Overall, the question of whether to continue treatment for cancer in a patient with concomitant COVID-19 should be individualized to that patient, with currently no specific recommendations on whether to continue or discontinue cancer therapy due to the vast array of cancer diagnoses, treatment options, and current comorbidities.¹ Currently, the CDC recommends that patients with cancer and COVID-19 have a conversation with their health care provider or care team to discuss the individual level of risk based on the patient’s current condition, treatment, and the level of transmission within their community.¹

As a pharmacist, it is extremely important to counsel patients with cancer who develop COVID-19 to keep taking medications or not alter their treatment plan without first talking to their health care provider. Although no guidelines are published on oncology pharmacy practice in the COVID-19 context, the French Society for Oncology Pharmacy advocates that hospital and community pharmacists be especially alert to the use of OTC treatments and complementary and alternative medicines, as the pandemic encourages self-medication, which can lead to drug-related problems and herb-drug interactions.¹⁵

ANNA LEE PETIT, is a PharmD candidate at Auburn University Harrison School of Pharmacy in Alabama; MARILYN N. BULLOCH, PHARMD, BCPS, FCCM, is an inpatient pharmacist in Tuscaloosa, Alabama, and a faculty member with Auburn University in Arkansas.

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