Treatments Linked to Death in COVID Patients With Thoracic Cancers

Jennifer Smith

June 29, 2020

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Past treatment may affect the risk of death among patients with thoracic malignancies who develop COVID-19, according to data from the TERAVOLT registry.

Prior treatment with steroids, anticoagulants, chemotherapy alone, or chemotherapy plus immunotherapy were all associated with an increased risk of death, but prior treatment with tyrosine kinase inhibitors or immunotherapy alone were not.

At the same time, there were no COVID-19–directed treatments that seemed to affect the risk of death.

"When we look at therapies administered to treat COVID-19 … including anticoagulation, antibiotics, antivirals, hydroxychloroquine, we found that no particular therapy was associated with increased chance of recovery from COVID-19," said Leora Horn, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Dr. Horn presented these findings as part of the American Society of Clinical Oncology virtual scientific program.


The TERAVOLT registry is the brainchild of Marina Garassino, MD, of the National Cancer Institute of Milan. On March 15, Dr. Garassino emailed colleagues around the world with the idea of starting the registry. Within 5 days, the final protocol was approved, and the first patient was entered onto TERAVOLT.

In creating a registry, Dr. Garassino and colleagues wanted to "determine the demographic factors, comorbidities, cancer characteristics, and therapies that place patients with thoracic malignancies who develop COVID-19 most at risk for hospitalization and death," Dr. Horn said.

Other goals of the registry are "to understand the clinical course of patients with thoracic malignancies who are infected by SARS-CoV-2, to provide practitioners with real-time data on therapeutic strategies that may impact survival, [and] to evaluate the long-term impact on cancer outcomes related to care adjustments and delays in patients with thoracic malignancies," she added.

Dr. Garassino presented the first analysis of TERAVOLT data at the AACR virtual meeting I in April. Results were recently published in The Lancet Oncology as well. That analysis included 200 patients, 98% of whom were from Europe, and the median follow-up was 15 days.

Baseline Characteristics and Outcomes

Dr. Horn's updated analysis included 400 patients with a median follow-up of 33 days from COVID-19 diagnosis. The data encompassed patients from North and South America, Europe, Africa, Asia, and Australia.

Of the 400 patients, 169 had recovered, 141 had died, and 118 were still in the hospital at the time of analysis. In all, 334 patients (78.3%) required a hospital admission, and 33 (8.3%) were admitted to the ICU. The median length of hospitalization was 10 days.

Across the three outcome groups (recovered, died, ongoing), the median age was 67-70 years. Most patients had non–small cell lung cancer (74.5%-81.9%), and most had stage IV disease (61.4%-76.8%).

A majority of patients were male (63.3%-70.2%), and most were current or former smokers (77.5%-86.9%). The median body mass index was 24-25 kg/m2, and 35%-46.4% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.

Most patients (82.2%-90.7%) had COVID-19 diagnosed via real-time polymerase chain reaction, although some patients were diagnosed via clinical findings alone (3.1%-5%).

"[R]egardless of outcome, the most common presenting symptom was fever, cough, or dyspnea," Dr. Horn noted.

As for complications of COVID-19, 71% of patients who died had pneumonitis/pneumonia, 49.6% had acute respiratory distress syndrome, 14.9% had multiorgan failure, 12.1% had sepsis, and 5.7% had coagulopathy.

Among recovered patients, 59% had pneumonitis/pneumonia, 4.1% had acute respiratory distress syndrome, 3% had coagulopathy, 0.6% had sepsis, and none had multiorgan failure.

Patients who recovered were more likely to have no comorbidities at baseline, and 31.2% of patients who died had at least one comorbidity. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease, vascular disease, diabetes, and renal insufficiencies.

Prior Treatments and COVID Therapy

Among patients who died, 33.4% were on ACE inhibitors or angiotensin II receptor blockers, 27% were on anticoagulants, and 23.4% were on steroids (the equivalent of at least 10 mg of prednisone per day) at the time of COVID-19 diagnosis. Among recovered patients, 20.7% were on ACE inhibitors or angiotensin II receptor blockers, 18.3% were on anticoagulants, and 14.2% were on steroids at the time of COVID-19 diagnosis.

"When we look at cancer therapy in the last 3 months, we can see that, regardless of outcome, the majority of patients had either not been treated or were on first-line therapy at the time of their COVID-19 diagnosis," Dr. Horn noted.

Among patients who died, 46.8% had received chemotherapy, 22% had received immunotherapy, 12.8% had received targeted therapy, and 9.2% had received radiotherapy. Among recovered patients, 33.7% had received chemotherapy, 26.6% had received immunotherapy, 19.5% had received targeted therapy, and 14.2% had received radiotherapy.

COVID-19–directed treatments included anticoagulation, antibiotics, antivirals, antifungals, steroids, interleukin-6 inhibitors, and hydroxychloroquine. Use of these therapies was similar among patients who recovered and patients who died.

Factors Associated With Death

In all, 79.4% of deaths were attributed to COVID-19, 10.6% were attributed to cancer, 8.5% were attributed to cancer and COVID-19, and 1.4% of deaths had an unknown cause.

In a univariate analysis, baseline characteristics associated with an increased risk of death were age of 65 years or older (P = .0033), one or more comorbidity (P = .0351), and ECOG performance status of 1 (P < .0001). Therapies associated with an increased risk of death in a univariate analysis included steroids (P = .0186), anticoagulation (P = .0562), and either chemotherapy alone or chemotherapy plus immunotherapy (P = .0256).

In a multivariate analysis, age over 65 years (P = .018), ECOG performance status of 1 (P < .001), prior use of steroids (P = .052), and receipt of chemotherapy alone or in combination with immunotherapy (P = .025) were all associated with an increased risk of death.

"There is no impact of gender [sex], body mass index, smoking status, stage, or type of cancer on risk of death," Dr. Horn said. "Therapy administered to treat COVID-19 is not significantly associated with outcome."

"The impact of COVID-19 infection on cancer management and outcomes must be evaluated," she added. "Data collection is ongoing, with additional analysis and studies planned to look at patient and provider perception of COVID-19 and the impact it has had on cancer care."

Strengths and Limitations

There are several limitations to findings from the TERAVOLT registry, according to invited discussant Giuseppe Curigliano, MD, PhD, of the University of Milan.

He said the results are limited by the differences in triage decisions between European and other centers, the fact that most patients in TERAVOLT were hospitalized, the high proportion of patients with stage IV non–small cell lung cancer, and methods of data collection and analysis.

"There is no real-time data capture, no auditing, no standardized outcome definitions, and CRFs [case report forms] had a lot of limitations," Dr. Curigliano said. "We have multiple biases, including selection bias, recall bias, confounding by indication, and changes in practice or disease evolution."

Dr. Curigliano noted, however, that TERAVOLT is the largest real-world dataset of patients with COVID-19 and thoracic malignancies.

Furthermore, results from TERAVOLT correspond to results from the CCC-19 registry. Data from both registries suggest that older age, the presence of comorbidities, higher ECOG performances status, and chemotherapy alone or in combination with other therapies are associated with increased mortality among patients with cancer and COVID-19.

The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer. Dr. Horn disclosed relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and a variety of other pharmaceutical companies. Dr. Curigliano disclosed relationships with AstraZeneca, Boehringer Ingelheim, Ellipses Pharma, and a variety of other pharmaceutical companies.

SOURCE: Horn L et al. ASCO 2020, Abstract LBA111.

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