Why Is COVID-19 More Aggressive in Patients with Cancer?

July 2020 Vol 11, No 7

Categories:

COVID-19

At the 2020 virtual meeting of the American Association for Cancer Research (AACR), a group of oncologists working in different hot spots around the world gave a snapshot of wisdom gleaned from their experience thus far. COVID-19 is a rapidly evolving field, and the summaries below represent experience as of the time of the meeting—late April 2020. AACR will host another COVID-19 and Cancer session at the Virtual Meeting II, June 22-24, 2020, as well as a 2-day Virtual Conference in July devoted solely to this topic based on abstracts and peer review.

Thus far, COVID-19 appears to be more aggressive and more lethal in patients with cancer, as suggested by 2 papers from Wuhan, China, but the experience in Europe suggests that this is due to comorbidities, type of cancer, and receiving chemotherapy rather than the cancer itself.

Experience in China

Two recently published studies from Wuhan found that cancer patients who contracted COVID-19 had a more aggressive course of COVID-19 disease and worse outcomes than noncancer patients.

A retrospective cohort of patients with cancer and confirmed COVID-19 infection from 3 designated hospitals in Wuhan, from January 13 to February 26, 2020, was described by Li Zhang, MD, Tongji Hospital, Wuhan.

This analysis included 28 COVID-19 cancer patients with a median age of 65 years; 60% were male. Among these patients, 25% had lung cancer and 28.6% were assumed to be infected from hospital-associated transmission. Fifteen patients (53.6%) developed severe COVID- 19 infection, and 28.6% died—a much higher rate of death than reported in noncancer patients, she said.

Risk factors for developing severe COVID-19 disease included receiving anticancer treatment within the past 14 days from the infection diagnosis and lung involvement. Treatment with immune checkpoint inhibitors was not associated with more severe events or death in cancer patients in this small series.

A second presentation focused on the first large cohort study on this topic—a multicenter retrospective study that included 105 cancer patients and 536 nonmatched noncancer patients who served as controls, with confirmed COVID- 19 infection. The presenting author was Hongbing Cai, MD, Zhongnan Hospital of Wuhan University, China.

The study showed that COVID-19–infected cancer patients had a higher risk of more severe outcomes; in particular, patients with lung cancer, hematologic cancers, or metastatic cancer had the highest risk of severe events. Nonmetastatic cancer patients had similar outcomes as those observed in noncancer patients. Surgery, but not radiation therapy, increased the risk of severe events compared with noncancer patients. There were no data presented on chemotherapy and COVID-19.

These studies from China had somewhat different findings than those by European investigators.

Global Registry of Thoracic Cancer

The TERAVOLT global registry of patients with thoracic malignancies and COVID-19 includes 21 countries, and more are expected to join. Data from this registry suggest that patients with cancer have a high death rate from COVID-19—not from cancer.

“Things are moving very quickly. We are registering about 70 new cases per week from all over the world, and many centers decided to join this registry,” said Marina Chiara Garassino, MD, medical oncologist at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, who presented early data from the global registry.

Among the first 191 thoracic cancer patients with COVID-19 infection enrolled in the registry, the death rate was 34.6%. The most frequent complications were pneumonia and pneumonitis (79.6%), acute respiratory distress syndrome (ARDS; 26.8%), multiorgan failure (7.6%), and sepsis (5.1%). The majority of deaths were attributed to COVID-19, not to cancer.

“Our data suggest an unexpectedly high mortality among patients with thoracic cancers, with a 34.6% death rate. In the large majority, the cause of death is attributed to COVID-19 infection, not to cancer. We have checked this on a case-by-case basis,” she said. “No comorbidities were significantly associated with a higher risk of death, and no anticancer treatments were associated with higher mortality in this preliminary analysis,” she added.

The data gathered on this first set of patients enrolled in the registry showed that 83.8% had comorbidities (more than one-quarter had 3 or more comorbidities), and 73.9% of patients were on anticancer treatment that included chemotherapy, immunotherapy, and combinations of these agents. Although 76% of patients required hospitalization for COVID-19 infection, only 8.8% were admitted to the ICU, and mechanical ventilation was used in 2.5%, which probably reflects shortages. “With a strong united community, we were able to activate a global registry and provide preliminary data in only 1 month in the absence of dedicated funding. My final thought is that it’s important that you don’t go this alone; join the registries. We need to work together to get these data really quickly to help our patients,” Dr Garassino said.

Experience in France

“ECOG Performance Status >1 and hematologic malignancies were the strongest predictors of clinical worsening in cancer patients with COVID-19,” said Fabrice Barlesi, MD, PhD, medical director of Gustave Roussy Institute, Paris, France.

This study was based on 137 patients with cancer and confirmed COVID-19 infection treated at Gustave Roussy. The majority of these patients (84%) had solid tumors, while 16% had hematologic cancer.

In univariate analysis and multivariate analysis, treatment with chemotherapy within the past 3 months was associated with a higher risk of clinical worsening compared with not receiving chemotherapy in that period. Treatment with immunotherapy or targeted therapy within the past 3 months did not have an impact on clinical worsening.

The higher risk of COVID-19 worsening or death with chemotherapy was confined to those with active advanced disease. “This means that we may continue to treat patients with localized disease with cytotoxic chemotherapy in the adjuvant or neoadjuvant setting. We have to pay attention to factors like this when deciding how to treat and manage patients with cancer and COVID-19,” Dr Barlesi said.

Melanoma and Beyond

Paolo A. Ascierto, MD, Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, National Tumor Institute Fondazione G. Pascale, Naples, Italy, said the highest priority should be given to patients with stage III melanoma eligible for curative resection, patients requiring resection for oligometastatic disease, and for surgical management of complications from surgery.

According to Dr Ascierto, follow-up after surgery should be done via telemedicine. Clinic visits should be postponed, especially if there is no evidence of disease.

Adjuvant treatment can be delayed for up to 12 weeks, and he recommended longer dosing intervals for checkpoint inhibitors, such as every 6 weeks for pembrolizumab and every 4 weeks for nivolumab.

“For patients with metastatic disease, no stops or delays are advised for targeted therapies or immunotherapies for unresectable stage II or IV melanoma. If possible, use a longer treatment schedule,” he said.

Experience in Spain

Carlos Gomez-Martin, MD, PhD, medical oncologist at University Hospital 12 de Octubre, Madrid, Spain, explained how strategies evolved at his institution after the first diagnosis of COVID-19 in a cancer patient on March 5. That prompted efforts to contain the outbreak by testing all patients and caregivers suspected of having the infection or who were in contact with anyone who had the disease. Outpatient visits were limited, and telemedicine was introduced for cancer-related symptom management.

Cancer patients with suspected or confirmed COVID-19 infection were transferred to designated wards with multidisciplinary staff dedicated exclusively to the care of these patients.

This strategy kept the oncology admissions for cancer patients with COVID-19 steady over that period, while the number of total COVID-19–related admissions at the hospitals rapidly increased to almost 1200 patients.

“Multidisciplinary care is the cornerstone of treatment and should involve specific antiviral treatment, supportive care, close monitoring of inflammatory parameters, and appropriate use of anticoagulants, given the risk of thromboembolic complications in this disease,” he said.

Between March 9 and April 19, 2020, 287 cancer patients were screened with reverse transcription polymerase chain reaction (RT-PCR) for COVID-19 in the outpatient clinic and emergency department; 26% had a positive test. Ninety patients were admitted to the hospital; 55 had a positive RT-PCR test. The other 35 patients admitted had a risk factor for poor outcome.

He presented data on the first 63 patients who were admitted. Sixteen (25%) of the 63 patients died of COVID-19 infection, with a mean overall survival of 12.4 days. Thirty-four patients developed respiratory failure, and 24 developed ARDS; 66% of these patients died. Mean time from onset of symptoms to respiratory failure was 7.02 days, and mean time to hospital discharge was 14.8 days.

Death occurred in 40% of lung cancer patients (29% with metastatic disease), 100% with bilateral pneumonia, 62% with hypertension, and 31% in those with prior steroids >10 mg. Nine of 63 patients developed venous thromboembolism.

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Last modified: July 9, 2020

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