Lung Cancer Mortality Rates Have Significantly Declined Due to New Treatments

Mortality rates from non-small cell lung cancer (NSCLC) have significantly declined in the United States in recent years. According to study published in the New England Journal of Medicine, the primary reason is the recent advances in treatment options for NSCLC.

Researchers at the National Cancer Institute (NCI) analyzed data for both NSCLC and small-cell lung cancer (SCLC), which account for 76% and 13% of lung cancer in the United States, respectively.

"Reduced tobacco consumption in the United States has been associated with a progressive decrease in lung cancer deaths that started around 1990 in men and around 2000 in women. Until now, however, we have not known whether newer treatments might contribute to some of the recent improvement," said Douglas R. Lowy, MD, NCI deputy director and co-author of the study, in a press release. "This analysis shows for the first time that nationwide mortality rates for the most common category of lung cancer, non-small cell lung cancer, are declining faster than its incidence, an advance that correlates with the [US Food and Drug Administration] approval of several targeted therapies for this cancer in recent years."

Over the past decade, new treatments for NSCLC have been released, some of which target the genetic changes seen in some NSCLC tumors and immune checkpoint inhibitors that support the immune system in preventing NSCLC; however, few treatment advances have been developed for SCLC.

Death records generally do not differentiate between NSCLC and SCLC, however the cancer diagnosis records compiled by NCI's Surveillance, Epidemiology, and End Results (SEER) cancer registry program do make such distinctions. This allowed the researchers to then make estimates regarding the mortality rate trends of these specific lung cancer subtypes by connecting the lung cancer death records of patients to the incidence data for these patients in the SEER database.

The researchers then assessed the data and observed that deaths from NSCLC decreased more quickly than the decrease in NSCLC incidence. Additionally, the decrease in deaths was associated with a significant improvement in survival.

For example, deaths from NSCLC among men decreased 3.2% annually during the period between 2006 and 2013, and 6.3% annually between 2013 and 2016. However, incidence of NSCLC decreased 1.9% annually between 2001 and 2008, and 3.1% annually between 2008 and 2016.

During these periods, 2-year survival among men with NSCLC increased from 26% for patients diagnosed in 2001 to 35% for those diagnosed in 2014. Additionally, such improvements in 2-year survival were seen among women, as well as all races/ethnicities, despite concerns regarding the disparities that may be caused by the high cost of the newer cancer treatments.

In contrast to the improvements seen among patients with NSCLC, 2-year survival for patients with SCLC was largely unchanged, with the decrease in deaths from SCLC observed by the researchers shown to correspond with the decrease in its incidence.

For example, deaths among men with SCLC declined 4.3% annually and incidence declined 3.6% annually, with findings remaining similar among women. The researchers noted that the reduced mortality from SCLC primarily reflects declines in incidence, which can largely be associated with the reduction of smoking in these populations.

The researchers found that the accelerating decline in NSCLC mortality, which started in 2013, is connected to the point when clinicians began to routinely test patients for genetic alterations targeted by newly approved drugs. This routine testing began after the National Comprehensive Cancer Network recommendation in 2012 that all patients with nonsquamous NSCLC undergo genetic testing. For this reason, the rate of genetic testing for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements increased substantially, as both of these gene rearrangements are targeted by newer treatments.

Additionally, since immune checkpoint inhibitors were not widely used during the period of the study’s analysis, the researchers said that most of the survival benefit may be attributable to effective EGFR or ALK inhibitors or other advances in therapy. With the significant effect of immune checkpoint inhibitors on NSCLC survival, the researchers added that the trend toward improved survival should continue beyond 2016.

"The survival benefit for patients with non-small cell lung cancer treated with targeted therapies has been demonstrated in clinical trials, but this study highlights the impact of these treatments at the population level," said study lead Nadia Howlader, PhD, of NCI's Division of Cancer Control and Population Sciences, in the press release. "We can now see the impact of advances in lung cancer treatment on survival."

REFERENCE

New treatments spur sharp reduction in lung cancer mortality rate. National Cancer Institute; August 12, 2020. eurekalert.org/pub_releases/2020-08/nci-nts080720.php. Accessed August 17, 2020.