CCC-19 Registry Data Show Increased COVID-19–Associated Mortality in Patients With Cancer

Brian I. Rini, MD

The mortality rate with COVID-19 appears to be higher in patients with cancer—especially those with lung cancer—compared with the general population, according to updated data released from several registries reported during the AACR Virtual Meeting on COVID-19 and Cancer, and several factors associated with mortality are beginning to emerge.¹

“Several ongoing registries are collecting a wealth of data on patients with cancer who have COVID-19, and we’re starting to see data [from these efforts reported]. The COVID-19 mortality rate in patients with cancer appears to be higher than that of the general population,” Brian I. Rini, MD, professor of medicine and chief of clinical trials at Vanderbilt-Ingram Cancer Center, said in a presentation during the meeting.

“Specifically, [mortality] was 16% per the most recent update from the COVID-19 and Cancer Consortium (CCC-19), and patients with lung cancer appear especially vulnerable, according to data from TERAVOLT,” Rini added. “Several factors relating to COVID-19 mortality in patients with cancer are also being reported; some are cancer-related, such as the status of their cancer and perhaps performance status, and others are unrelated, such as age or gender.”

In his presentation, Rini walked through the different registries that are collecting data regarding COVID-19–associated mortality in patients with cancer, shared data that are available thus far, and highlighted a new study that will provide longitudinal data on a large cohort of patients with active cancer who are receiving treatment.

Updated Data from CCC-19

Early on in the COVID-19 pandemic, many investigators had hypothesized that patients would be at increased risk of adverse outcomes with the virus because of advanced age, the presence of comorbidities, increased contact with the health care system, immune alterations due to their cancer and/or treatment, and decreased performance status, according to Rini.

To better understand how the virus was impacting patients with cancer, the CCC-19 was created. The consortium started as a grassroots effort by a few participating institutions to collect granular data on patients with cancer and their outcomes with the virus. The effort has since grown tremendously, with over 114 participating institutions, to date.

The initial analysis of data collected from the registry were presented by Jeremy L. Warner, MD, of Vanderbilt University Medical Center, in a presentation during the 2020 ASCO Virtual Scientific Program and showed that patients with progressive cancer were 5.2-times more likely to die within 30 days of being diagnosed with COVID-19 versus patients in remission or without any evidence of disease.² Additionally, the risk for death was found to be 1.79 times greater for patients with stable cancer versus those with no evidence of disease. The data were simultaneously published in The Lancet.

During the 2020 AACR Virtual Meeting on COVID-19 and Cancer, Rini reported an update as of the third data lock, which was June 26, 2020. At that time, a total of 2956 surveys had been submitted to the registry; after certain surveys were excluded, investigators considered a total of 2749 patients in their analysis.

Results showed that at a median follow-up of 30 days, the mortality rate was 16% (n = 433); notably, the rate reported in the initial analysis was 13%, according to Rini. Some of the major outcomes measured included mechanical ventilation (12%) and intensive care unit (ICU) admission (16%). The composite outcome rate was 29%; this was defined as death, severe illness requiring hospitalization, ICU admission, or mechanical ventilation. Moreover, almost half of the patients required oxygen (45%) and the majority, or 60%, were hospitalized.

When looking at mortality for select patient subgroups, the rate of mortality per global statistics was 5%. Notably, patients who had an ECOG performance status of 0 and did not have any comorbidities were found to have a relatively low mortality rate, at 4%. “We saw an increasing mortality rate for males, those with progressing cancer, older patients, those with and those with worse performance status,” said Rini. “If you combine these adverse risk factors, you get into very high mortality rates.”

When looking at mortality with regard to cancer type, breast cancer had the largest cohort of patients (n = 502), but a lower mortality rate, at 8%. Patients with prostate cancer (n = 39/392), plasma cell dyscrasias (n = 26/137), colorectal cancer (n = 36/186), and lymphoma (n = 57/263) had higher mortality rates, at 18%, 19%, 19%, and 22%, respectively. Notably, patients with lung cancer (n = 61/237) had the highest mortality rate, at 26%.

Investigators also collected data on some of the factors associated with 30-day mortality. Updated data, which differed from what had originally been published in The Lancet, revealed non-Hispanic black patients had a higher risk than white patients. Hematologic malignancies have also become a significant factor with an adjusted odds ratio (AOR) of 1.8 compared with solid tumors. “You also see a worsening performance status for a cancer that is present or is certainly progressing, increasing a patient with cancer's risk of dying from COVID-19,” added Rini.

Notably, certain factors did not reach statistical significance; these included obesity (AOR, 1.23), cytotoxic chemotherapy versus none (AOR, 1.14), noncytotoxic therapy versus none (AOR, 0.75), and recent surgery (AOR, 1.05). “In the present analysis of almost 3000 patients, I think this provides reassurance that cancer care can, and should, continue for these patients,” stressed Rini.

TERVALOT

Another effort spearheaded by Leora Horn, MD, MSc, of Vanderbilt-Ingram Cancer Center, and Marina Chiara Garassino, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori is TERAVOLT, a global registry collecting characteristics and outcomes of patients with thoracic cancers affected by COVID-19.

Data reported from 400 patients analyzed showed a very high mortality rate of 35.5%, with 78.3% of patients requiring hospitalization and 8.3% of patients admitted to the ICU.³ “Many of the patients in this registry were from Italy at the time of their crisis and so they may not have had access to ICU admission; however, I think the high mortality rates seen in CCC-19 is also reinforced here,” explained Rini.

In a multivariate analysis of risk factors linked with death from COVID-19, investigators also reported that older age (HR, 1.70) and worsening performance status (HR, 2.14) as adverse risk factors. Steroids received prior to COVID-19 diagnosis was determined to be of borderline significance (HR, 1.49), and when looking at oncologic therapy received, investigators noted that receiving chemotherapy versus other types of treatment was another significant risk factor.

ESMO-CoCARE

The ESMO-CoCare registry is an international collaborative project that was launched to rapidly gather data from healthcare professionals on treatment approaches, specifically focused on the impact of COVID-19 on patients with cancer with suspected or confirmed infection.⁴

To be eligible for inclusion, patients must have a solid or hematologic malignancy and laboratory confirmed or clinical diagnosis of COVID-19. The exploratory end points for this effort include major demographic features of patients with cancer and COVID-19; the prevalence of major comorbidities in this patient population; the proportion of patients with cancer who experience a severe event overall; the proportion of patients with cancer and COVID-19 who received systemic treatment in the last 2 months prior to infection; risk factors predictive of severe clinical course; biomarkers predictive of cancer treatment–specific adverse effects in this patient population; prognostic factors; and cancer- and COVID-19–specific mortality.

“This registry is just up and running; it has not yet reported data,” noted Rini.

ASH Research Collaborative COVID-19 Registry for Hematology

The ASH Research Collaborative COVID-19 Registry for Hematology is another ongoing effort. The registry is intended to serve as a global public reference tool that will capture information on patients with hematologic malignancies who test positive for COVID-19 and those who have experienced a post–COVID-19 hematologic complication.⁵ Interestingly, as data are inputted into the platform, real-time observational summaries are produced and made available.

“Topline data from when I accessed this dashboard a few days ago show a fairly high mortality rate. Although this is a small number of patients, it again reinforces with new findings from CCC-19,” said Rini. “Hematologic malignancies [can be] a risk factor.”

ASCO Survey on COVID-19 in Oncology Registry

ASCO has also launched a registry initiative which will aim to assist the cancer community in developing a better understanding regarding patterns in symptoms and severity of COVID-19 in patients with cancer, and importantly, how the virus is affecting the delivery of cancer care, and thus, patient outcomes.⁶ The registry will collect baseline and follow-up data on how COVID-19 impacts care for this patient population through the pandemic and into 2021.

Specifically, the data collected will include treatment approaches, cancer status, changes to cancer evaluation and treatment plans in patients infected with the virus, status of infection, and cancer.

As of June 25, 2020, 37 practices in 22 states are enrolled and a total of 131 patients have baseline data available.

“What’s different about the ASCO registry is that it is looking in a more granular way at the delivery of cancer care compared with the other registries that I have discussed so far,” said Rini. “Are patients having delay of cancer care? Are they having avoidance of cancer care? This is about the delivery of care as much as the outcomes of COVID-19 infection in this population.”

Launch of NCCAPS: A Longitudinal Natural History Study

In the NCI COVID-19 in Cancer Patients Study (NCCAPS), investigators will follow patients and collect medical and other data over time to learn more about the virus and its symptoms to ultimately assist the cancer community in better managing patients with cancer who are infected with the virus in the future.⁷

In order to be eligible for the study, patients must be receiving active treatment for metastatic cancer within the past 6 weeks, including chemotherapy, immunotherapy, treatment with monoclonal antibodies, targeted therapies, endocrine therapy, or radiation therapy. They could have received neoadjuvant or adjuvant treatment for nonmetastatic stage I to III disease within the past 6 weeks. They were permitted to have undergone allogenic stem cell transplant or have received CAR T-cell or other modified cellular therapy at any time; have received active treatment or prophylaxis for graft versus host disease; or have undergone autologous bone marrow transplant within the past 2 years.

The planned accrual for the trial is 2,000 patients, and investigators will follow outcomes for up to 2 years. Data will be collected on pre-existing comorbidities, cancer type and treatment, demographic factors, COVID-19 course, short- and long-term cancer outcomes, and any modifications made to cancer treatment.

“There’s also a large effort being made to collect imaging scans just prior to COVID-19 diagnosis and what would be done normally for cancer staging or during the course of caring for patients for COVID-19,” said Rini. “The unique, special part of this study is that biospecimens are being collected, and we'll look at serology, such as the development of antibodies over time, cytokine abnormalities—especially in patients who have more acute inpatient courses—DNA-based genome wide association studies, as well as coagulation parameters.”

The study has been activated at over 500 sites, added Rini, and accrual was just started a couple of weeks ago. “This will accrue rapidly over the next several months,” projected Rini.

References

1. Rini B. Understanding the impact of COVID-19 in cancer patients through the COVID-19 and Cancer (CCC-19) and other COVID-19 consortiums. Presented at: 2020 AACR Virtual Meeting on COVID-19 and Cancer; July 20-22, 2020. Virtual. Accessed July 22, 2020.
2. 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). J Clin Oncol. 2020;38(suppl 18):LBA110. doi:10.1200/JCO.2020.38.18_suppl.LBA110
3. 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. J Clin Oncol. 2020;38(suppl 18):LBA111. doi:10.1200/JCO.2020.38.18_suppl.LBA111
4. ESMO-CoCARE Registry. ESMO. Accessed July 22, 2020. https://bit.ly/2ZOPxh5.
5. ASH RC COVID-19 Registry for Hematology. ASH Research Collaborative. Accessed July 22, 2020. https://bit.ly/3huP7CG.
6. ASCO Survey on COVID-19 in Oncology Registry. ASCO. Accessed July 22, 2020. https://bit.ly/3eLJ22Q.
7. NCI COVID-19 in Cancer Patients Study (NCCAPS). National Cancer Institute. Accessed July 22, 2020. https://bit.ly/39vZcwp.