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

TOP - July 2020, Vol 13, No 4

At the 2020 virtual American Association for Cancer Research (AACR) annual meeting, part I, a team of oncologists from different COVID-19 hotspots around the world gave a snapshot of wisdom gleaned from their experience thus far. Understanding of COVID-19 is rapidly evolving; the summaries below represent the experience as of late April 2020.

AACR will host another session on this topic at its part II of the virtual meeting in late June and in July. Thus far, COVID-19 appears to be more aggressive and more lethal in patients with cancer, as suggested by 2 presentations from Wuhan, China, but the experience in Europe suggests that increased mortality may be linked to certain comorbidities, the type of cancer, and use of chemotherapy rather than the cancer itself.

The Chinese Experience

Two recently published studies from Wuhan showed that patients with cancer and COVID-19 had a more aggressive course of COVID-19 and worse outcomes than patients without cancer.

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

This analysis included 28 patients with COVID-19 and cancer (median age, 65 years); 60% of the patients were male. Among these patients, 25% had lung cancer and 28.6% were assumed to be infected from hospital-associated transmission. A total of 15 (53.9%) patients had severe COVID-19 infection, and 28.6% died, which is a much higher mortality rate than was reported in patients without cancer, Dr Zhang said.

The risk factors for severe COVID-19 infection included receiving anticancer treatment within the past 14 days from the infection diagnosis and lung involvement. Treatment with an immune checkpoint inhibitor was not associated with more severe events or with increased mortality in patients with cancer in this small series.

A second presentation focused on the first large cohort study on this topic. This multicenter retrospective study included 641 patients with confirmed COVID-19 infection; of these, 105 patients had cancer and 536 did not have cancer and served as controls. Hongbing Cai, MD, of Zhongnan Hospital in Wuhan University, presented the study results.

The study showed that patients with COVID-19 infection and cancer had higher risks for more severe outcomes than those without cancer; in particular, patients with lung cancer, hematologic cancer, or metastatic cancer had the highest risk for severe events.

Patients with nonmetastatic cancer had similar outcomes as patients without cancer. Surgery, but not radiation therapy, increased the risk for severe events compared with patients without cancer. No data were presented on chemotherapy and COVID-19 infection.

These studies from China had slightly different findings from the studies conducted by European investigators.

Global Registry of Thoracic Cancer

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

“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, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, who presented early data from the global registry.

Among the first 191 patients with thoracic cancer and 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 (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,” Dr Garassino 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% of patients had comorbidities—25% of patients had ≥3 comorbidities—and 73.9% of patients were receiving anticancer treatment that included chemotherapy, immunotherapy, or a combination of these agents. Although 76% of patients required hospitalization for COVID-19 infection, just 8.8% were admitted to the intensive care unit, and mechanical ventilation was used in only 2.5% of the patients, which may reflect shortages in ventilators.

“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.

COVID-19 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, Gustave Roussy, Villejuif, France.

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

In univariate and multivariate analyses, treatment with chemotherapy within the past 3 months was associated with an increased risk for clinical worsening compared with not receiving chemotherapy in that period. Treatment with immunotherapy or targeted therapy within the past 3 months did not result in clinical worsening.

The increased risk for COVID-19–related worsening or death with chemotherapy was confined to patients with active advanced cancer.

“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 Surgery

Paolo A. Ascierto, MD, Director, Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy, said the highest priority should be given to patients with stage III melanoma who are eligible for curative resection, patients requiring resection for oligometastatic disease, and for the 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 Dr Ascierto recommended longer dosing intervals for those receiving checkpoint inhibitors, such as every 6 weeks for pembrolizumab (Keytruda) and every 4 weeks for nivolumab (Opdivo). “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 advised.

Key Risk Factors

Carlos Gomez-Martin, MD, PhD, Gastrointestinal Cancer and Early Clinical and Translational Research Units, Octubre University Hospital, Madrid, Spain, explained how strategies evolved at his institution after the first diagnosis of COVID-19 in a patient with cancer.

That prompted efforts to contain the outbreak by testing all patients and caregivers suspected of having the infection or those who were in contact with anyone who had the disease. Outpatient visits were limited, and telemedicine was introduced for cancer-related symptom management. Patients with cancer and 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 patients with cancer and 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,” Dr Gomez-Martin said.

Between March 9 and April 19, 2020, 287 patients with cancer were screened for COVID-19 and 26% of patients had a positive test. A total of 90 patients were admitted to the hospital; 55 had a positive RT-PCR test. The other 35 patients had a risk factor for poor outcome.

Dr Gomez-Martin presented data on the first 63 patients who were admitted. Of these patients, 16 (25%) died from COVID-19 infection, with a mean overall survival of 12.4 days. In all, 34 patients had respiratory failure and 24 had acute respiratory distress syndrome from the infection; 66% of these patients died. The mean time from the onset of COVID-19 symptoms to respiratory failure was 7.02 days, and the mean time to hospital discharge was 14.8 days.

The mortality rate was 40% in patients with lung cancer (29% with metastatic disease), 100% with bilateral pneumonia, 62% with hypertension, and 31% in patients who received previous treatment with steroids of >10 mg. Of the 63 admitted patients, 9 developed venous thromboembolism.

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