COVID-19 Presents an Opportunity for Precision Medicine to Play Expanded Role in Care

The crisis of coronavirus disease 2019, also known as COVID-19, presents a set of unprecedented circumstances to the health care community. The disease has a particular impact on patients with cancer and their oncology care teams who are trying to maintain the right balance between the use of immunosuppressive treatment and risk of cancer progression. Wenhua Liang, PhD, and colleagues analyzed the risk for severe COVID-19 in patients with cancer.1 They reported that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. They emphasized that patients with malignancy had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer to prioritize treatment versus risk of death and adverse outcomes. Patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (3 of 4 patients [75%]) of clinically severe events than did those not undergoing chemotherapy or surgery, observed by logistic regression (odds ratio, 5.34; 95% CI, 1.80-16.18; P = .0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities.

The authors of this study have proposed 3 major strategies for treating patients with cancer in the COVID-19 crisis. The first approach is an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with COVID-19, especially in older individuals or those with other comorbidities.

Oncologists and institutions caring for these patients face the continued challenges of administering treatment while simultaneously reducing the risk of complications in the event they end up contracting COVID-19. Stopping chemotherapy may be an option for patients in complete remission on maintenance therapy. In those patients, we may be able to switch chemotherapy from intravenous to oral therapies. This change would decrease the frequency of clinic visits. A chemotherapy break may be an option when feasible. Delays or modifying adjuvant treatment may be balanced with the risk of recurrence. The prophylactic growth factors and antibiotics in high-risk chemotherapy regimens is of paramount importance. When the absolute benefit of adjuvant chemotherapy may be quite small, and if non-immunosuppressive options are available (eg, hormonal therapy in estrogen receptorpositive early-stage breast cancer), risk of COVID-19 infection may be considered as an additional factor in weighing the patient’s available treatment options.

The Role of Precision Medicine

Providers caring for patients with cancer undergoing cytotoxic chemotherapy need to consider changing their treatment plan when feasible to reduce the risk of life-threatening complications as well as reducing the frequency of their clinic visits. Targeted therapies are approved for a number of aggressive cancers from non–small cell lung cancer, stage IV melanoma, to acute myeloid and lymphoid leukemia. These therapeutic options offer an opportunity to consider treatment of patients with the likelihood of a better response while at the same time increasing dose density and intensity without raising the toxicity profile.

Precision medicine–guided targeted therapies as well as immunotherapy may have a special role in identifying patients who may need cancer treatment. Most targeted agents are orally administered. The toxicity and adverse event profiles of many orally administered targeted therapies is significantly different from chemotherapy. A much higher complication rate from cytotoxic chemotherapy places patients with cancer at a much higher risk of complications from COVID-19 infection. Rigorous biomarker testing and appropriate therapeutic choice should be considered in this patient population, especially in the face of a global pandemic.

Assessing Cancer by Treatment Priority Determination: Top, Intermediate, and Low Priority

Instead of an arbitrary approach, a system to determine the priority for consultation and treatment of patients with cancer may provide a consistent approach for all patients and providers (TABLE).² It is also important to avoid, as much as possible, having different levels of care. We recommend following an “assessment for patients with cancer and treatment priority determination” that would assist cancer clinics and decision makers in the management of these patients. Given the dynamic situation, it is likely that this will vary from day to day, and daily accommodation reassessment may be required. The patient priority assessment and classification would allow flexibility determined by the local circumstances and available resources. The local or regional circumstances and the availability of resources may influence a cancer clinic’s ability to follow the criteria.

A Brief Look Back

This virus was previously referred to as novel betacoronavirus severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2).³ What started in early December 2019 with 3 patients diagnosed with unexplained pneumonia in the Wuhan province of China has led to a global pandemic. At the time this article was written, more than 3 million cases have been reported and 207,973 deaths across Europe, the Americas, Western Pacific, Eastern Mediterranean, Southeast Asia, and Africa are attributed to the disease.⁴ The United States alone has 1,005,147 cases and 57,505 deaths.⁵

In March 2020, the World Health Organization declared COVID-19, caused by SARS-CoV-2, a public health emergency of international magnitude and a global pandemic.⁶ According to the World Health Organization, the definition of pandemic is a worldwide spread of a new disease for which most people do not have immunity.

A sudden surge in the cases of COVID-19 due to the pandemic, along with efforts to contain it, has led to multiple challenges that no country has experienced in the last several decades. The global pandemic from COVID-19 poses a unique set of challenges not only for patients with cancer who need their treatment, but also for caregivers, oncologists, and the overall care team. It is recognized that there is a need to treat patients with cancer during a pandemic, due to their immunocompromised state from the nature of their disease or type of treatment they are receiving. Further, it is of paramount importance that the oncology care team develop and evolve a systemic approach that prioritizes patients, disease, and types of treatment. So far, the efforts of organizations and individual oncologists are being rapidly outpaced by the increasing number of patients with COVID-19. It is likely that this will be a dynamic situation that will vary each day.

Deaths from COVID-19 have been caused by multiple organ dysfunction. This observation might be attributable to the widespread distribution of angiotensin-converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.^7,8 Patients with cancer are more susceptible to infection than individuals without cancer because of their malignancy and anticancer treatments, such as chemotherapy.⁹ These patients might be at increased risk of COVID-19 and have a poorer prognosis.

Rapid growth in the number of patients with COVID-19 symptoms has led to capacity pressures to the health care system on a local, regional, and national level. Cancer clinics and hospital inpatient and outpatient areas have started experiencing capacity challenges. Patients with cancer are faced with difficult decisions and anxieties related to the risks of treatment versus exposure and increased risk of contracting COVID-19. It is expected that the COVID-19 global pandemic will hit in 1 or more waves. At the peak of the COVID-19 wave, a significant portion of hospital or clinic staff will be ill or unavailable to work (eg, due to school closures, family obligations, fear, disease, illness, etc.

An Indelible Mark

COVID-19 has left an indelible mark on the history of the world. Although the death toll world wide approaches 140,000, it is only through humanity’s collective ingenuity and compassion to care for one another will we weather this pandemic. We are making daily progress and we applaud all health care workers who find themselves on the frontlines against this disease.

_References:

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_{2. Dietz JR, Moran MS, Isakoff SJ, et al. Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. the COVID-19 pandemic breast cancer consortium [published online ahead of print, 2020 Apr 24]. Breast Cancer Res Treat. 2020;1-11. doi:10.1007/s10549-020-05644-z}

_{3. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513. doi:10.1016/S01406736(20)30211-7.}

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_{7. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273. doi: 10.1038/s41586-020-2012-7}

_{8. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-637. doi: 10.1002/path.1570}

_{9. Kamboj M, Sepkowitz KA. Nosocomial infections in patients with cancer. Lancet Oncol. 2009;10(6):589-597. doi: 10.1016/S1470-2045(09)70069-5}