NCI's Sharpless: COVID-19 Could Halt Streak of US Cancer Mortality Gains

Months of deferred screenings or delayed treatment due to coronavirus disease 2019 (COVID-19) could reverse the US streak in improved cancer mortality that has lasted more than 25 years, the director of the National Cancer Institute (NCI) said Saturday.

Norman E. “Ned” Sharpless, MD, who served briefly as acting FDA commissioner in 2019, opened the virtual session on "Cancer and COVID-19" during the American Society of Clinical Oncology (ASCO) 2020 annual meeting with a sober assessment of COVID-19’s effects on both clinical care and cancer research.

His talk preceded presentations on some of the earliest findings about the effects of COVID-19 on cancer: It appears patients treated with chemotherapy for lung or thoracic cancer shortly before being diagnosed COVID-19 face a higher risk of death, and so do patients with cancer who take the hydroxychloroquine (HCQ) and azithromycin combination.

The separate data sets shape an emerging picture of what patients with cancer face under COVID-19: They are more likely to be older or have underlying health problems, which are known to make the virus more deadly.

And, as Jeremy L. Warner, MD, an associate professor at Vanderbilt University Medical Center explained, patients may be immunosuppressed from the treatment or the disease itself, and have more frequent contact with the health care system than people without cancer.

Deferred Care Will Come at a Price

The decision to preserve hospital and clinical capacity was “necessary and important” as COVID-19 peaked this spring, Sharpless said, “But all this deferred care—it’s going to have costs for patients with cancer. It may mean more cancer suffering outcomes for our patients. What we don’t know yet is the scale of these bad outcomes.”

Each year, he said, NCI works with the American Cancer Society and others to publish an annual report on the state of cancer, and the declining mortality rates have become an annual “shot in the arm” for cancer researchers. “My fear is that diminished cancer care will produce a negative impact on these cancer statistics of relevance to the public health. And we expect to see these trends play out over several years,” he said. “We cannot escape this reality.”

Research is taking a hit, too, as patient accruals in NCI trials have fallen off pace, and Sharpless said he hears similar reports about industry-sponsored trials. What is filing the gap somewhat, he said, are aggressive efforts to start trials to understand COVID-19's affect on patients with cancer. He highlighted 2 groups presenting results during the session, as well as registries set up by ASCO and the American Society of Hematology.

Last week marked the launch of the NCI COVID-19 in Cancer Patients Study (NCCAPS) that will enroll 2000 patients with cancer who are diagnosed with COVID-19. “We aim to conduct the study at more than 1000 sites,” he said. “We need to know as much about the impact of COVID-19 on cancer patients in Montana as we do about those in New York. What have you learned about the impact of the virus on patients across racial and ethnic groups?"

Sharpless pointed out the NCI effort “is not a registry,” but a trial approved by an institutional review board; investigators will seek patient consent to collect samples, analyze biomarkers, and develop germline sequencing of patients.

Patients who participate will be required to have regular health care visits, where the facility will collect blood samples and copies of routine imaging scans for up to 2 years. “It's important to note that participation this study will not require additional visits to the hospital or other facilities,” Sharpless said. “Much of the data will be collected electronically and some of the tests will be part of the patient's routine care.”

Results From TERAVOLT

Prior smoking history or lung damage are among the characteristics that put patients with thoracic cancer at particular risk from COVID-19, according to insights gleaned from 400 patients records in the Thoracic canERS international CoVid 19 COLlaboraTion (TERAVOLT) registry.¹ Thoracic cancers include lung, mesothelioma, carcinoid tumors, and thymic neoplasms.

According to the researchers, use of chemotherapy within 3 months of a COVID-19 diagnosis turned out to have a particularly strong association with early death: a 64% increased risk of dying from the virus. The effect of chemotherapy was seen whether or not patients also had other therapies, such as immunotherapy, which showed up as a potential risk factor in an earlier study.

Of the 144 patients who died, 79.4% (112 patients) died from COVID-19, while 10.6% (15 patients) died from cancer. Treatment with anticoagulants and corticosteroids were also linked to increased death risk, adding to existing concerns about the use of corticosteroids for patients with chronic disease. More data will be needed to draw any firm conclusions about the use of anticoagulants.

Lead author Leora Horn, MD, commented on the speed with which the research effort has taken shape. “In less than a week we had a study enrolling patients,” said Horn, who is the Ingram associate professor of Cancer Research and the director of the Thoracic Oncology Program at Vanderbilt University Medical Center. “We have seen clinical trials being funded, approved and begin enrolling patients within weeks, when it can often take months or years to get approval for a trial.”

Cancer and the Cocktail

Cancer patients with COVID-19 who were treated with both HCQ and azithromycin were 3 times more likely to die during the 30 days after they were diagnosed, according to findings² presented by Warner, lead author of the study from the COVID-19 and Cancer Consortium, which launched its registry March 15.

Warner, speaking earlier in the week, cautioned that the association is of “uncertain validity” and may stem from residual confounding. “For example,” he said, “patients receiving this combination were more likely to have severe disease or more likely to be hospitalized.”

The researchers also reported that neither drug was associated with an added mortality risk when they were taken alone.

After some statistical adjustments, the researchers found that patients with worsening cancer were 5 times more likely to have died within 30 days of their COVID-19 diagnosis than patients in remission or no evidence of disease.

Of the 928 people with cancer and COVID-19 who were included in study, 121 (13%) died within 30 days of their COVID-19 diagnosis, according to findings that Warner presented in the preview. The written abstract made available to the media had slightly different numbers: 1108 cases and 106 deaths, or 10.4% of the total cases.

In their analysis of the cases and deaths, the researchers found that factors associated with a 30-day mortality risk were worsening, or progressing cancer, active cancer, older age, male sex, and being a former smoker.

Only 3 of the 121 deaths that Warner discussed in his video presentation were of people with no comorbidities. Of the 466 who were hospitalized, 106 died.

References

1. Horn L, Whisenant JG, Torri V, et al. Thoracic Cancers International COVID-19 Collaboration (TERAVOLT): Impact of type of cancer therapy and COVID therapy on survival. Presented at: The American Society of Clinical Oncology 2020 Annual Meeting; Alexandria, VA: May 29-31. Abstract LBA 111.

2. Warner JL, Rubinstein S, Grivas P, et al. Warner JL, Rubinstein S, Grivas P, et al. Clinical impact of COVID-19 on patients with cancer: Data from the COVID-19 and Cancer Consortium (CCC19). Presented at: The American Society of Clinical Oncology 2020 Annual Meeting; Alexandria, VA: May 29-31. Abstract LBA 110.