Norman E. “Ned” Sharpless, MD, discusses the efforts that The National Cancer Institute has made to combat the coronavirus disease 2019 pandemic.
The National Cancer Institute (NCI) has made several efforts to combat the coronavirus disease 2019 (COVID-19) pandemic, according to Norman E. “Ned” Sharpless, MD, such as investigating anticancer agents to treat the disease, increasing flexibility with regard to clinical trials, and conducting critical serology research to increase understanding and inform future approaches.1
On November 3, 2020, the World Health Organization reported that more than 3.3 million new cases of COVID-19 had been reported worldwide in the past week alone.2 As of November 1, 2020, approximately 46 million cases, along with 1.2 million deaths had been reported worldwide. In the United States, the Centers for Disease Control and Prevention has reported around 9,463,782 cases since January 21, 2020; 629,390 if those cases were identified in the past week.3
With efforts such as the COVID-19 and Cancer Consortium (CCC19), investigators have been able to collect important data on adult patients with a history of or who currently have an invasive solid tumor or hematologic malignancy and have also been diagnosed with COVID-19.
Results from this effort have revealed some factors that are associated with increased 30-day all-cause mortality in patients with cancer and COVID-19, including increasing age, male sex, smoking status (former smoker vs never smoker), cancer status (present, stable, or responding, and present, progressive disease vs remission or no evidence of disease), treatment with hydroxychloroquine plus azithromycin versus treatment with neither, and 2 or more comorbidities requiring treatment.4 These efforts have also yielded factors that are not associated with mortality such as race and ethnicity, obesity, type of malignancy, type and recency of anticancer treatment, and recent surgery.
“As many of you are aware, the NCI has significant expertise…and a lot of external capabilities to do cutting-edge research in an emergency setting,” said Sharpless, director of the NCI, in a virtual presentation during the 38th Annual CFS®. “As such, I think it was natural when the pandemic really got going, that the NCI was asked to step in and help provide some scientific response.”
A modeling effort performed last spring and published in Science utilized the NCI’s Cancer Intervention and Surveillance Monitoring Network (CISNET) to better understand cancer control interventions in terms of prevention, screening, and treatment and their impact on population trends in both incidence and mortality.5
“We asked the CISNET investigators to consider what we thought at that time were quite significant disruptions to cancer care, [in terms of] screening, diagnosis, and delayed therapy,” said Sharpless. “We asked [them to make] what we thought were significant assumptions about disruption of care [so we can gain some insight on] what would happen to cancer mortality over the next decade.”
Investigators looked specifically at breast and colorectal cancers, as the CISNET models were advanced for these 2 tumors, according to Sharpless. When looking at the modeled cumulative excess deaths from these disease from 2020 to 2030, investigators projected that there would be an excess of 10,000 deaths, or a 1% increase in mortality over the next decade, said Sharpless. The same disruptions are believed to be at play in other malignancies, as well.
“We feel that the assumptions we made about the disruptions to care, were, if anything, conservative estimates and the disruptions that we're actually seeing in hospitals across the country are greater than what we had predicted back then in June,” said Sharpless. “This is something that we all have to bear in mind. We need to share some collective responsibility [to determine] how to preserve the cancer care enterprise during a pandemic and ensure that we're not exchanging one public health crisis for another.”
In light of the pandemic, data have indicated that there has been a decline in cancer screening and diagnosis, along with decreased or deferred care; these disruptions will likely have long-term implications for cancer mortality, stressed Sharpless. To combat this, the oncology community needs to come together to find safe, innovative ways to prioritize care for patients with cancer, he added.
“We don’t want our patients to be at risk for COVID-19, nor their caregivers; however, we need to get back to business,” said Sharpless.
The NCI has made several efforts in response to the pandemic. These efforts range from repurposing anticancer drugs to treat COVID-19, to the launch of the NCI COVID-19 in Cancer Patients Study (NCCAPS), to providing guidance and special procedures for clinical trials in the field of oncology, to conducting SARS-CoV-2 serology research, and offering flexibilities and opportunities for grantees.
Repurposing Cancer Drugs to Fight COVID-19
Patients who have severe infection with COVID-19 have a hyperinflammatory immune response that is indicative of macrophage activation. BTK is known to influence macrophage signaling and activation. Bearing this in mind, the selective BTK inhibitor acalabrutinib (Calquence) was evaluated off-label in 19 hospitalized patients with severe COVID-19 infection; of these patients, 11 required supplemental oxygen, while 8 were on mechanical ventilation. In 10 to 14 days of treatment, acalabrutinib led to an improvement in oxygenation in most patients; this benefit was observed within 1 to 3 days of treatment and with no toxicity was observed.7
“Now, this agent is under exploration in 2 large randomized trials in Europe and the United States as a disease-modifying agent and for patients who may or may not get steroids depending on the clinical setting,” said Sharpless. “This is an example of the kind of scientific observation that comes out of the NCI; [this treatment] might make a difference for patients with [cancer and] COVID-19.”
Adapting Clinical Trial Efforts
In light of the pandemic, many laboratories had to close down, timelines for clinical trials were delayed, and several adjustments were required in order to continue the investigation of potentially life-saving drugs in patients who needed them most.
In recognition of the challenges posed by the pandemic with regard to clinical trials being performed in the United States, the NCI collaborated with the FDA to provide flexibility to their supported efforts. For example, patient care can now be transferred to different participating study sites. Also, local healthcare providers are able to provide study activities to encourage the continuity of care. Oral drugs may now be shipped from the NCI and trial sites directly to the study participant to decrease unnecessary risk. Moreover, remote informed consent via telephone has also become acceptable, in conjunction with a patient signature on a written document.
“We know that this has been a successful [effort]. Accrual on NCI therapeutic trials has largely returned to normal. Also, we have polled investigators and they really like some of these flexibilities,” said Sharples. “This is, perhaps, the silver lining of the pandemic. We've learned how to do trials in the modern era of Zoom chat and telehealth. We won’t forget those lessons. Many of these flexibilities will be good for clinical trials going forward and will affect how the NCI does business even after the pandemic is [over].”
NCCAPS Clinical Trial to Collect Longitudinal Data
NCCAPS is a natural history clinical trial of COVID-19 in patients with cancer. For the study, investigators are following patients and collecting relevant information over time to better understand how the virus and its symptoms develop and evolve.8 The objective of the trial is to help inform the future management of patients with cancer who are also diagnosed with COVID-19. The comprehensive dataset with collect information on cancers, treatments, symptoms, course, recovery, and comorbidities with longitudinal follow-up.
In the study, investigators will gather blood samples to estimate antibody response and genetic susceptibility. These samples will also be utilized for biomarker development. A total of 2000 patients are anticipated to be included in this trial.
“We launched this trial in about 6 weeks last spring and it is now open at nearly 1000 sites in the United States. It has begun fairly robust accrual for patients with a history of cancer and COVID-19 infection,” noted Sharpless. “We believe it will be very valuable to understand the
biomarkers that predict bad outcomes in patients with cancer, as well as to understand the longitudinal history of this disease, or the so-called long-haul COVID-19 conditions that we are now seeing in some patients.”
SARS-CoV-2 Serology Research Abounds
In October 2020, the NCI launched the Serological Sciences Network for COVID-19 (SeroNet), the goal of which was to increase the nation’s capacity for antibody testing and to assist the country’s research community to glean a better understanding of immune response to the virus.9
“The NCI has a long history in serology research, and it has a fantastic lab that does serology research for human papillomavirus vaccine response; it was 1 of the standard study labs for the World Health Organization and other international agencies,” said Sharpless. “When the pandemic began, we repurposed that lab to become a SARS-CoV-2 coronavirus lab…[We wanted to] create a network to increase capacity for coronavirus testing and serology testing in the United States.”
This initiative is anticipated to engage over 25 academic, government, and private sector biomedical research institutions to evaluate immune response to the virus as a means for producing rapid testing and developing novel therapeutics and vaccines.
To assist this initiative, Congress authorized $306 million for the NCI to develop, validate, improve, and apply serological testing and associated technologies, according to the NCI.
Flexibilities to Support Grantees During the Crisis
In light of the COVID-19 pandemic, the NCI has also channeled efforts into providing certain flexibilities to grantees who experienced disruptions to their research efforts.
“This has been [a] hard [time] for trainees who need to move to the next stage of their training or [who need to] get a job,” noted Sharpless. “This has also been difficult for scientists whose labs have been closed or whose clinical research efforts have been put on pause. The NCI, along with the broader National Institutes of Health, has been trying to send the message to grantees that we are going to allow every possible flexibility during the pandemic so that research can get back to normal as quickly as possible.”
Some of the flexibilities offered by the NIH include extending deadlines for applications, permitting institutions to use NCI grant funds to maintain salaries and stipends, extending project timelines and reporting requirements, extending eligibility periods for early-stage investigators and trainees, and carryover for institutional training grants with previous approval.
Outside of the COVID-19 pandemic, and with a goal to honor the 50th anniversary of the National Cancer Act of 1971, the NCI has announced that they seek to build a coalition of support for cancer research, which includes raising the payline to 15% by 2025.10
“This is a commemoration of an important milestone. All the progress we've made in the past 5 decades has been wonderful and important, but we still have much yet to do,” concluded Sharpless. “The NCI would like to see this become a joined moment for the community to start talking about the National Cancer Act and what it means for cancer research in general. The entire cancer research and care community should discuss this; it’s an opportunity to make clear to the public and Congress what we've accomplished and where else we can go next.”