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Christina Lau
13 Jul 2020

Prior treatment with chemotherapy alone, chemotherapy plus immunotherapy, steroids or anticoagulants is associated with an increased risk of death in patients with thoracic cancer who develop coronavirus disease 2019 (COVID-19), new data from the global TERAVOLT (Thoracic Cancers International COVID-10 Collaboration) registry have shown.

“However, prior treatment with immunotherapy or tyrosine kinase inhibitors [TKIs] alone was not associated with an increased mortality risk,” said investigator Dr Leora Horn of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, US, who presented the results at the American Society of Clinical Oncology 2020 Virtual Scientific Programme (ASCO 2020). [Horn L, et al, ASCO 2020, abstract LBA111]

The TERAVOLT registry is the first global registry established to understand the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. [http://teravolt-consortium.org/] The first analysis, in 200 patients followed up for a median of 15 days, showed a 33 percent death rate and a 10 percent rate of intensive care unit (ICU) admission. Smoking history was the only factor associated with an increased risk of death (odds ratio [OR], 3.18; 95 percent confidence interval [CI], 1.11 to 9.06) on multivariable analysis. [Garassino MC, et al, AACR 2020 Virtual Meeting I; Lancet Oncol 2020, doi: 10.1016/S1470-2045(20)30314-4]

Chemo, chemo + IO, steroids, anticoagulants linked to increased death

“The updated analysis included 400 patients from North and South America, Europe, Africa, Asia and Australia, who were followed up for a median of 33 days from COVID-19 diagnosis,” said Horn.

At baseline, 169 patients had recovered, 141 patients had died, and 118 remained hospitalized. The patients’ median age was 66.5–70 years. A majority of patients had stage IV cancer (61.4–76.8 percent), with non-small-cell lung cancer (74.5–81.9 percent) being the most common tumour type.

“The death rate was 35.5 percent. A majority [79.4 percent; n=112] of the deaths were due to COVID-19. Cancer accounted for 10.6 percent [n=15] of the deaths, while 8.5 percent [n=12] of the patients died due to cancer and COVID-19,” reported Horn.

“Use of chemotherapy alone or in combination with immunotherapy [p=0.0256] in the last 3 months, but not immunotherapy or TKIs alone, was associated with an increased risk of death from COVID-19,” she said. “Patients on steroids [>10 mg of prednisone or equivalent; p=0.0186] or anticoagulants [p=0.0562] at COVID-19 diagnosis were also at increased risk of death.”

On multivariate analysis, the hazard ratio (HR) for death from COVID-19 was 1.71 (95 percent CI, 1.12 to 2.63) for chemotherapy +/- other therapy vs no treatment, 1.64 (95 percent CI, 0.77 to 3.48) for chemotherapy +/- other therapy vs immuno-oncology (IO) or targeted therapy, and 1.04 (95 percent CI, 0.56 to 1.93) for IO or targeted therapy vs no treatment (p=0.025). The HR for death for steroid use prior to COVID-19 diagnosis was 1.49 (95 percent CI, 1.00 to 2.23; p=0.052).

Among patients who died, 46.8 percent had received chemotherapy in the last 3 months, while 22 percent and 12.8 percent had received immunotherapy and targeted therapy, respectively. “Regardless of outcome, most patients in the cohort were either receiving first-line cancer therapy or not receiving cancer therapy at the time of COVID-19 diagnosis,” noted Horn.

COVID-19 therapies: No impact on outcome

“Hospitalization was required in 78.3 percent [n=334] of the patients, while 8.3 percent [n=33] were admitted to ICU. The median length of hospitalization was 10 days,” said Horn.

The most common presenting symptoms of COVID-19 were fever (53.4–67.5 percent), cough (37.4–52.7 percent), and dyspnoea (39.8–78.0 percent). Among patients who died, the most common COVID-19 complications were pneumonitis/pneumonia (71.0 percent), acute respiratory distress syndrome (49.6 percent), multiorgan failure (14.9 percent) and sepsis (12.1 percent).

“Therapy administered to treat COVID-19 was not significantly associated with outcome,” reported Horn. “No particular therapy was associated with an increased chance of recovery from COVID-19.”

Patients who died and those who had recovered were given similar therapies to treat COVID-19. Antibiotics were the most commonly used (27 percent vs 27 percent), followed by anticoagulants (23 percent vs 24 percent), hydroxychloroquine (19 percent vs 23 percent), steroids (16 percent vs 10 percent) and antivirals (12 percent vs 14 percent).

Older age, ECOG PS, comorbidities: Baseline risk factors for death

On multivariate analysis, age ≥65 years (HR vs age <65 years, 1.70 ;95 percent CI, 1.09 to 2.63; p=0.018) and Eastern Cooperative Oncology Group performance status (ECOG PS) of 1 (HR vs ECOG PS 0, 2.14 ;95 percent CI, 1.11 to 4.11; p<0.001) were associated with an increased risk of death from COVID-19.

“Patients with ≥1 comorbidity at baseline also had an increased risk of death from COVID-19 [p=0.0351],” said Horn. “However, there was no impact of gender, BMI, smoking status, or stage or type of cancer on mortality risk.”

Other studies: Similar findings for chemo

The updated TERAVOLT findings are similar to those from a recent multicentre study in 205 cancer patients (lung cancer, 12 percent) with COVID-19 in Hubei, China. Over a median follow-up of 68 days, receipt of chemotherapy within 4 weeks before symptom onset was found to be a risk factor for death during hospitalization (OR, 3.51; 95 percent CI, 1.16 to 10.59; p=0.026). [Lancet Oncol 2020;21:904-913]

Similarly, a French single-centre study in 137 cancer patients with COVID-19 showed that use of chemotherapy within the last 3 months was significantly associated with clinical worsening (ie, need for oxygen supplementation of ≥6 L/min, or death due to any cause) (HR, 2.60; 95 percent CI, 1.32 to 5.13; p=0.006). However, use of targeted therapy or immunotherapy was not found to have an impact. [Barlesi F, et al, AACR 2020 Virtual Meeting I]

In contrast, a multicentre study in 105 cancer patients with COVID-19 in Wuhan, China, showed high rates of mortality (33.3 percent) and critical symptoms (66.7 percent) in those who had received immunotherapy within 40 days prior to onset of COVID-19 symptoms. [Cancer Discov 2020, doi: 10.1158/2159-8290]
“The impact of COVID-19 on cancer management and outcome must be evaluated. Data collection is ongoing, with additional analyses planned to evaluate patient and provider perception of the impact of COVID-19 on cancer care,” concluded Horn.

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