Lung Cancer Lessons from COVID-19

This year has brought with it many challenges, but perhaps the most prominent is the infectious disease pandemic that continues to rage on in the United States and around the world. The oncology community has risen up as a unified front in the battle against coronavirus disease 2019 (COVID-19), launching pivotal research efforts to better understand the enemy and collecting data to develop effective therapeutics to fill the treatment arsenal.

“2020 has been a stunning year for all of us to go through. We’ve learned a lot…I really respect all the healthcare workers who I have witnessed participate in the tremendous effort to protect and help our patients [with cancer] through the pandemic,” Balazs Halmos, MD, said in a closing presentation during the 15th Annual New York Lung Cancers Symposium.¹ “This year has been very hard—not just with COVID-19. We’ve also seen social injustices and racial inequalities [brought to light]. Hopefully, we will close the year learning from all of this.”

Halmos, a professor of medicine at Albert Einstein College of Medicine and director of the Thoracic Head and Neck Program at Montefiore Medical Center, went on to say that the pandemic is far from over. As of November 8, 2020, the Centers for Disease Control and Prevention have reported over 9,808,411 cases since January 21, 2020, with over 236,547 deaths.²

“[On Friday, November 6, 2020,] we just saw the largest number of cases to have been reported since the start of the pandemic—more than 100,000,” noted Halmos. “Fortunately, case fatality rates have been going down, but still, [we’re seeing] thousands of deaths per day. It’s not something that we want to witness. Hopefully, we’ll be better disciplined and [going forward] we’ll be able to make better sense of how to manage the pandemic as a country.”

Since the first potential case was reported in Wuhan, China, in December 2019,3 much has been learned about the disease on a global scale. For example, it is now understood that COVID-19 goes through a viral replication phase that leads to viral pneumonia, according to Halmos. In some patients, inflammatory conditions can then ensue, although this can potentially be controlled with certain therapeutics, such as antivirals and anti-inflammatory agents.

In October 2020, the FDA approved the first treatment for COVID-19: remdesivir (Veklury). The antiviral agent is indicated for use in adult and pediatric patients who are 12 years of age or older and weigh at least 40 kilograms, or around 88 pounds, for the treatment of the infection requiring hospitalization. The regulatory decision was based on data analysis yielded from 3 randomized, controlled trials.⁴

Insight Into the Montefiore Experience

Earlier on in the pandemic, investigators examined 218 patients with cancer and COVID-19 who received treatment within the Montefiore Health System between March 18, 2020, and April 8, 2020.5 Seventy-five percent (n = 164) of these patients had solid tumors, while 25% (n = 54) had hematologic malignancies. A little more than half, or 58% of these patients were male and 42% were female. The majority of patients were adult patients who had a median age of 69 years.

The mortality rate observed in this analysis was 28%. Moreover, mortality was observed to occur at higher rates in patients with lung cancers (55%), gastrointestinal cancers (GI; 38%, colorectal; 67%, pancreatic; 38%, upper GI) and gynecologic malignancies (38%). Patients who had genitourinary malignancies or breast cancer were found to have a relatively lower mortality rate, at 15% and 14%, respectively.

“Looking at the first 200-plus cases, we saw a tremendous mortality, of 28% or so, but admittedly, these were the first cases in the United States,” said Halmos. “Testing was not available. Patients had to be very symptomatic to deserve a test on a certain level. However, what I believe was more important was what we learned in terms of who is actually at risk for significant morbidity and mortality [from infection with the virus].”

Notably, the major associations of poor outcomes were primarily age and comorbidities. The median age of the deceased subgroup was 76 years versus 66 years in the nondeceased subgroup (P =.0006; Cochran-Armitage test). With regard to comorbidities, patients with cancer who were at an increased risk of dying from the virus included those who had concomitant heart disease and chronic lung disease. In a univariate analysis, diabetes and chronic kidney disease were not linked with increased mortality.

TERAVOLT Defines COVID-19 Outcomes in Thoracic Cancer

Through the global consortium TERAVOLT, the outcomes of patients with thoracic cancer who are infected with COVID-19 are under investigation. Investigators are also using these data to learn more about risk factors linked with mortality in this patient population.

Initial results from the global registry indicated that after a median follow-up of 15 days, only patients who were greater than 65 years of age were found to have increased morbidity from the virus; 33% of these patients had died from COVID-19—associated complications.⁶ Updated data presented during the 2020 ASCO Virtual Scientific Program, showed that chemotherapy administered within 3 months of a diagnosis of COVID-19 increased the risk of death in patients with thoracic cancer.⁷

As of July 15, 2020, 1012 patients from 20 countries have been entered into the registry. Data presented during the 2020 ESMO Virtual Congress revealed that patients who presented with pneumonia, consolidation, bilateral lung abnormalities, and pleural effusion were at increased risk of mortality.8 Data from a multivariate analysis showed that those 65 years of age or older, active smokers, those with a higher stage of cancer, an ECOG performance status of 2 or higher, and those who received steroids before diagnosis with the virus, all were at increased risk of death. Notably, treatment with chemotherapy and TKIs were not found to be associated with increased risk of mortality and patients who received immunotherapy appeared to be at a decreased risk of death.

"There seems to be an interesting signal that being on steroids at the time of COVID-19 infection is a risk factor and I would think that most likely, this is related to the reasons why a patient might be on steroids at the time,” said Halmos. “Also, we saw from this experience that smoking, prior steroids, age, and oncologic treatment like chemotherapy appear to be risk factors, but ECOG performance status seems to be the primary driving force of a patient's poor outcome.”

COVID-19 and Cancer Consortium Contributes to Greater Understanding of COVID-19

Formed on March 15, 2020, the COVID-19 and Cancer Consortium (CCC19) was formed to evaluate the clinical characteristics and course of disease in patients with COVID-19 who have a current or past cancer diagnosis.

Accrual to the registry began on March 17, 2020, and results from the initial analysis demonstrated that patients with progressive cancer were 5.2-times more likely to die within 30 days of diagnosis with COVID-19 versus those who were in remission or who had no evidence of disease.⁹ Moreover, the risk of death was found to be 1.79 times greater for patients who had stable disease versus those without evidence of disease.

“The most striking discovery from this cohort was really the incredible spectrum of morbidity that you can see in healthy patients with good performance status and no comorbidities. Cancer itself wasn’t a particular risk factor, although elderly patients with poor performance status do incredibly poorly,” said Halmos. “I believe this provided reassurance for us to be able to help patients with cancer who didn’t seem to fall in a major risk category, but also [help us] protect our patients with significant comorbidities and poorer performance status better.”

COVID-19 Research Efforts Abound in New York

“What I’ve learned through this experience is that oncologists in New York City are not a lazy bunch,” said Halmos. “It wasnt just us [from Montefiore] who contributed to this cohort experience or understanding about COVID-19. Every single major institution in the city has done something remarkable in terms of promoting knowledge [of this virus].”

Investigators from Memorial Sloan Kettering Cancer Center found that the virus was linked with high burden of severity in patients with lung cancer. Moreover, they showed that patient-specific features rather than cancer-specific features or treatments like immunotherapy were the greatest causes of severity.¹⁰

Additionally, researchers at Weill Cornell Medicine/NewYork-Presbyterian Hospital showed that patients with cancer and COVID-19 had similar outcomes to those without cancer, suggesting that a diagnosis of active cancer alone and recent anticancer agents does not necessarily predict for worse outcomes with the virus.¹¹

“Matthew Hirsch, MD, is leading national efforts in terms of immunology development, along with his colleagues at Mount Sinai,” added Halmos. “Deborah B. Doroshow, MD, PhD, has contributed majorly to the CCC19 study and [her team is] looking at cancer care disparities. This is important to look at, especially this year where we recognize so much in terms of racial inequalities and social injustice in the country.”

Collateral Damage Caused by the COVID-19 Crisis

Halmos went on to say that now that enough information has been gathered with regard to major risk factors and poor outcomes in patients with cancer who are infected with the virus, it’s important to be aware of others way in which the pandemic has affected this population.

“Cancer screening rates have dropped dramatically. [We saw around an] 80% drop off. [Rates are] slowly picking back up but the damage is going to be substantial for quite some time,” said Halmos. “The same thing happened with cancer research. [We saw a] 50% drop off in clinical trials accruals. All our academic and community oncologists [have been working very hard] to pick up the slack. We’re back at full pace in a way but certainly some opportunities have gotten lost. We need to keep up the effort.”

ASCO has also reported that 64% of Americans reported having a cancer screening test delayed or cancelled because of COVID-19.12 Reports from the United Kingdom Lung Cancer Coalition also indicated that the impact of the virus in England could lead to a decrease in lung cancer 5-year survival in the longer term¹ due to screening pilots have been put on pause, individuals with potential symptoms not engaging with the healthcare system, a change in treatment schedule with reduced levels of chemotherapy and surgery, social distancing measures potentially impacting palliative care support, and some research efforts put on pause.

A Snapshot into the Impact of COVID-19 on the NYU Thoracic Oncology Program

Vamsidhar Velcheti, MD, associate professor in the Department of Medicine at NYU Grossman School of Medicine and the director of the Thoracic Med Oncology Program at NYU Langone, shared further insight on the impact of COVID-19 during the peak of the pandemic on the Thoracic Oncology program at his institution.

“We had a significant drop in our bronchoscopies and lung cancer surgeries. We also saw a pretty significant drop in clinical trial accrual, as well. There was a time when there was a significant strain on the hospital resources and outpatient clinics where we were very understaffed and we were very worried about the impact of COVID-19 on our patients,” said Velcheti. “We questioned whether it was safe to treat our patients through such a pandemic; [we didn’t want to] put them at a higher risk for infections.”

Following this, Velcheti noted a substantial increase in rebound in terms of outpatient appointments. Patients have also returned to being on systemic therapies and clinical trial accruals that has gone back to prepandemic levels.

“I think in my experience from the time of surge is if we can keep our patients safe by following protocols and guidelines, we should be able to treat most of our patients through this pandemic, added Velcheti.

“I completely agree,” Halmos noted. “I believe that all of us are working very hard to help our patients through these waves of COVID-19 and we really need to be skilled surfers. Whatever the wave brings us, we have to help our patients with cancer get through it and receive the proper attention and treatment [that they need].”

Personal Protective Equipment at Montefiore

At Montefiore, investigators developed the cancer patient’s personal protective equipment (PPE) in an effort to ensure the safe treatment of patients with cancer during the pandemic. In terms of prevention, appointments were conducted through the use of telemedicine, when possible. For frail and elderly patients, providers considered holding treatments and procedures until absolutely necessary.

In terms of protection, proper precautions were put in place throughout the healthcare system, treatment regimens were altered within reason, and patients with COVID-19 infection were separated from other patients in the hospital, said Halmos.

However, Halmos stressed that the majority of patients with cancer will be hurt more by withholding treatment for this disease than they would from infection with the virus. Bearing this in mind, practices have been put into place to allow for continued cancer care, testing has been integrated into procedures, and clinical trials have been reactivated.

The Battle Is Not Over

Despite all of the advances that have been made in understanding the impact of the infectious disease on patients with cancer, much more will need to be done to win the fight against the virus. Halmos closed his presentation by quoting Albert Camus: “What’s true of all the evils in the world is true of plague as well. It helps men to rise above themselves.”

References

1. Halmos B. Lessons for lung cancer from the pandemic. Presented at: 15th Annual New York Lung Cancers Symposium; November 7, 2020; Virtual. Accessed November 9, 2020.

2. CDC COVID data tracker: United States COVID-19 cases and deaths by state. Centers for Disease Control and Prevention. Updated November 8, 2020. Accessed November 9, 2020. https://bit.ly/32ulDj8.

3. Timeline of WHO’s response to COVID-19. World Health Organization. June 29, 2020. Accessed November 9, 2020. https://bit.ly/2U6CTXb.

4. FDA approves first treatment for COVID-19. News release. FDA. October 22, 2020. Accessed November 9, 2020. https://bit.ly/2JVmEdL.

5. Mehta V, Goel S, Kabarriti R, et al. Case fatality rate of cancer patients with COVID-19 in a New York hospital system. Cancer Discov. 2020;10(7):935-941. doi:10.1158/2159-8290.CD-20-0516

6. Garassino MC. TERAVOLT (Thoracic cancERs international coVid 19 cOLlaboraTion): first results of a global collaboration to address the impact of COVID-19 in patients with thoracic malignancies. Presented at: the 2020 AACRAnnual Virtual Meeting I; April 27-28, 2020. Session VCTPL09.

7. Horn L, Whisenant JG, Torri V, et al; TERAVOLT Consortium Investigators. Thoracic Cancers International COVID-19 Collaboration (TERAVOLT): Impact of type of cancer therapy and COVID therapy on survival. J Clin Oncol. 2020;38(suppl 15):LBA111. doi:10.1200/JCO.2020.38.15_suppl.LBA111

8. Espinar JB, Torri V, Whisenant J, et al. Defining COVID-19 outcomes in thoracic cancer patients: TERAVOLT (Thoracic cancERs international coVid 19 cOLlaboraTion). Ann Oncol. 2020;31(suppl 4):LBA75. doi:10.1016/j.annonc.2020.08.2316

9. 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

10. Luo J, Rizvi H, Preeshagul IR, et al. COVID-19 in patients with lung cancer. Ann Oncol. 2020;31(10):1386-1396. doi:10.1016/j.annonc.2020.06.007

11. Brar G. Pinheiro LC, Shusterman M, et al. COVID-19 severity and outcomes in patients with cancer: a matched cohort study. J Clin Oncol. Published online September 28, 2020. doi:10.1200/JCO.20.01580

12. National survey reveals racial differences in perceptions of inequities in health care and concerning delays in cancer screenings amid COVID-19. News release. ASCO. October 1, 2020. Accessed November 9, 2020. https://bit.ly/2JJeCEq.

This article was originally published on OncLive as, "Halmos Highlights Lessons Learned From the COVID-19 Crisis in Lung Cancer."