Solange Peters, MD, PhD
“The distressing intersection of COVID-19 and cancer requires the use of large registries to acknowledge diversity,” stated Solange Peters, MD, PhD, President of the European Society for Medical Oncology (ESMO), in her keynote speech at the American Association for Cancer Research (AACR) Virtual Meeting: COVID-19 and Cancer.1 Dr. Peters is Head of the Medical Oncology Service and Chair of Thoracic Oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters provided an update of the COVID-19 and Cancer Consortium (CCC19) cohort study across North and South America. Currently, the CCC19 has about 2,956 patients in the registry. At the meeting, Dr. Peters presented updated data on 2,186 patients with invasive cancer and laboratory-confirmed COVID-19 (unpublished data at the time of the meeting). These data represent patients entered in the registry between March 17, 2020, and June 26, 2020.
“This is the third look at the CCC19 data,” she told listeners. About 47% of patients had mild COVID-19 infection, 40% had moderate infection, and 12% had severe infection. In addition, 51% were in remission from their cancer, 28% had stable cancer or cancer responding to therapy, and 11% had actively progressing disease. The majority of patients had solid tumors (81%).
“Our findings strongly indicate that the role of emerging treatments requires formal prospective trials in the future.”— Solange Peters, MD, PhD
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Overall mortality for all patients with cancer included in the CCC19 cohort is 16%, whereas that figure is anywhere from 2% to 7% in the general population, depending on the geographic area and the study. Progressing cancer accounts for 26% of mortality; age over 75, for 27%; Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more, for 35%; age over 75 plus intubation, for 64%; and ECOG performance status of 2 or more with intubation, for 75%.
Mortality data for patients with specific cancers included the following: lung cancer 26%, lymphoma 22%, colorectal cancer 19%, plasma cell dyscrasias 19%, and breast cancer 8%. Selected factors associated with 30-day all-cause mortality adjusted for age, sex, obesity, recent surgery, geographic region, ECOG performance status, and cancer status included older age and male sex, which accounted for about 40% to 50% more deaths, respectively. Non-Hispanic Blacks had a 56% higher mortality compared with non-Hispanic Whites, and mortality associated with hematologic malignancy was about 80% higher than in those with solid tumors. Patients with an ECOG performance status of 1 had an 80% higher mortality than those with an ECOG performance status of 0; and those with an ECOG performance status of 2 or more have a 4.2 times higher likelihood of dying vs those with an ECOG performance status of 0.
If cancer is present and stable, the chance of dying is almost 50% higher vs no evidence of disease (remission). If cancer is progressing, the chance of dying is almost three times higher vs in remission or no evidence of disease.
The updated CCC19 data showed that of 2,186 patients enrolled in the database, 1,321 did not have any treatment; of those who were treated, 69% of patients were exposed to remdesivir, 5% to tocilizumab, and 41% to “other” treatments.
“Most patients were exposed to more than one treatment,” Dr. Peters noted. Patients with cardiovascular comorbidities were less likely to be exposed to hydroxychloroquine and azithromycin. Those living in the Western United States were more likely to receive remdesivir.
“COVID-19 has ushered in a lack of appropriate review and editorial rigor, even among elite medical journals, notably regarding the expertise of reviewers.”— Solange Peters, MD, PhD
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“Severe COVID-19 infection is, of course, correlated with higher exposure to COVID-directed treatments compared with mild and moderate COVID-19 infection,” Dr. Peters noted. “It was very important and disappointing to document for the first time that non-Hispanic Blacks had reduced exposure to remdesivir.”
“The 30-day all-cause mortality was associated with treatment exposure. High-dose hydroxychloroquine plus other treatments significantly increased mortality compared with other treatments or untreated patients, even if the most severely ill patients were excluded. Remdesivir alone was associated with decreased 30-day mortality compared with positive controls, with a similar trend compared to untreated negative controls. High-dose corticosteroids plus any other therapy were associated with increased 30-day mortality compared with positive and negative controls. We did not see the benefit of corticosteroids shown in other series,” she continued.
“Putting all of this in perspective, our findings strongly indicate that the role of emerging treatments requires formal prospective trials in the future,” Dr. Peters stated. She added that other COVID-19 and cancer registries include ESMO C0-Care, “a little sister of CCC19,” TERAVOLT, and many national initiatives globally.
TERAVOLT data presented by Dr. Peters demonstrated that in 400 patients with thoracic cancer and COVID-19, mortality was 35.5% (n = 141). Death due to COVID-19 occurred in 79.4% of these patients, and death due to cancer, in 10.6%; death due to both COVID-19 and cancer occurred in 8.5%. Admission to the intensive care unit (ICU) was required in 8.3%, and mechanical ventilation was needed in 5%.
In a multivariate analysis of TERAVOLT data, age, ECOG performance status, exposure to steroids prior to COVID-19 infection, and administration of chemotherapy with or without other treatments were all statistically associated with an increased risk of death, whereas immunotherapy or targeted therapy did not correlate with a higher risk of death.
Among 581 patients with thoracic cancers and COVID-19 included in TERAVOLT, 11% had small cell lung cancer (SCLC). An even higher mortality—61%—was found in those with SCLC. Among these patients, COVID-19–related death occurred in 36%, and only 14% were admitted to the ICU.
Lessons From COVID-19 Crisis
“We have learned humbling lessons from this crisis, and there were missed opportunities,” Dr. Peters continued.
“Authors have learned not to rush to publication before ensuring the source of data is appropriate. The flood of preprints without undergoing peer review is a major source of concern. COVID-19 has ushered in a lack of appropriate review and editorial rigor, even among elite medical journals, notably regarding the expertise of reviewers,” she said.
Going forward, Dr. Peters called for international collaboration on prospective series and large randomized trials. “We need to rethink cancer care altogether during the COVID-19 pandemic. We need to prioritize patients with cancer for treatment—according to whether treating the patient for cancer is a high, medium, or low priority,” she told the audience.
ESMO is working on adapting guidelines for 27 tumor types for inclusion on its website, using the priority rating as follows: high priority requires immediate intervention; medium priority means patients can wait 6 weeks for cancer intervention without a major impact; low priority indicates the patient’s condition is stable enough to wait for the end of the COVID-19 pandemic.
Other ESMO initiatives include an ESMO patient guide on how COVID-19 will impact patient care and a resilience taskforce survey to determine how oncology professionals have been affected by COVID-19. Of 1,570 respondents to the survey, 67% reported a change in their professional duties since the COVID-19 pandemic. The most common change was remote consultations (ie, telemedicine). More than 75% reported concern about personal safety at work.
Dr. Peters emphasized that the COVID-19 pandemic will exacerbate the gender gap and other inequities in cancer care. “Women represent 70% of health-care workers, and the burden of care may be higher for them than for men. In addition to their professional responsibilities, many women are also caregivers at home. Social distancing measures and child care services are affecting the work/life balance for women,” she noted.
“Previously, we showed that women were underrepresented in oncology journals, and now they are publishing less during the pandemic and publishing less about the pandemic. Women accounted for about 34% of all authors during the COVID-19 pandemic, and the number is lower when women are first authors. ESMO is trying to address possible gender differences during the pandemic through a very large international survey. Additionally, ESMO is aiming at identifying new ways to support oncologists. One way is to transform several meetings into virtual or hybridmeetings,” Dr. Peters stated.
ESMO is also working on solutions to drug shortages, which have been exacerbated during the time of COVID-19. “This requires concerted action at the international level. Many medicines affected by shortages don’t have effective alternatives,” she noted.
“The causes of medicine shortages are complex and multifactorial and cannot be solved by one country alone. Only a supranational solution can help mitigate the situation caused by shortages of inexpensive essential medicines,” Dr. Peters said.
DISCLOSURE: Dr. Peters has received institutional honoraria from AstraZeneca, Bristol Myers Squibb, Illumina, MSD, Novartis, Pfizer, Roche, and Takeda; has served in a consulting or advisory role for AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo, Debiopharm, Illumina, Incyte, Janssen, Lilly, Merck Serono, MSD, Novartis, Pfizer, Pharma Mar, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, Takeda, and Vaccibody; has received institutional research funding from Amgen, AstraZeneca, Biodesix, Bristol Myers Squibb, Boehringer Ingelheim, Illumina, Iovance, Lilly, Merck Serono, MSD, Novartis, Pfizer, and Roche; and has been reimbursed for travel, accommodations, or other expenses by Bristol Myers Squibb, Incyte, MSD, Roche, and Sanofi.
Photo of Dr. Peters courtesy of GO2Foundation for Lung Cancer.