Non-small cell lung cancer mortality rates decline sharply amid advances in treatment
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Non-small cell lung cancer mortality decreased substantially among the general U.S. population between 2013 and 2016, according to results of a retrospective study published in The New England Journal of Medicine.
The decline likely can be explained by a reduction in NSCLC incidence, as well as advances in treatment, including the introduction of targeted therapies, researchers noted.
“No one is discounting the role that decreased rates of smoking over many years in the United States has had on the falling mortality over time, but our research brings to light some other important factors,” Nadia Howlader, PhD, mathematical statistician in the division of cancer control and population sciences at NCI, told Healio. “Lung cancer screening rates also remained low and steady during the study period and did not contribute to these results.”
Overall lung cancer mortality has been declining in the U.S. for several years; however, subtype-specific mortality trends at the population level have been difficult to track because death certificates do not indicate cancer subtype.
The approval of targeted therapies and immunotherapies has led to major improvements in treatment of NSCLC — which accounts for 76% of all U.S. lung cancer cases. Conversely, advances in treatment of small cell lung cancer, which represents 13% of cases, have been limited.
Howlader and colleagues linked lung cancer deaths to incident cases in SEER cancer registries to determine population-level mortality trends attributed to specific subtypes. The researchers also assessed lung cancer incidence and survival according to cancer subtype, sex and calendar year.
Results showed NSCLC mortality decreased even faster than its incidence, and the decrease appeared associated with a substantial improvement in survival. This improvement in mortality corresponded to the approval of targeted therapies, researchers noted.
Incidence-based NSCLC mortality among men decreased by 6.3% (95% CI, 3.4-9) annually from 2013 to 2016, compared with a decrease of 3.2% (95% CI, 2.5-4) annually from 2006 to 2013. Meanwhile, incidence decreased by 3.1% (95% CI, 2.8-3.3) annually from 2008 to 2016, compared with a more gradual decrease of 1.9% (95% CI, 1.6-2.2) annually from 2001 to 2008.
Incidence of NSCLC among women remained steady from 2001 to 2006 before decreasing by 1.5% (95% CI, 1.3-1.7) annually from 2006 to 2016. Incidence-based mortality for women declined 2.3% (95% CI, 1.8-2.8) annually between 2006 and 2014 and 5.9% (95% CI, 1.3-10.2) annually from 2014 to 2016.
Researchers estimated that the greater reductions in mortality than incidence in more recent periods equates to an estimated 6,800 deaths of lung cancer among men and 3,200 deaths among women that have been delayed in the U.S. from 2014 to 2016.
Corresponding 2-year relative survival improved from 26% among men and 35% among women diagnosed with NSCLC in 2001, to 35% among men and 44% among women diagnosed in 2014. Researchers observed this improvement in survival across all races and ethnic groups.
Mortality from small cell lung cancer declined as a result of declining incidence, with no improvement in survival and limited treatment advances for this subtype during the period.
“A few new immunotherapies are coming for small cell lung cancer, so it will be interesting to see if the rates for that [malignancy] come down, as well, in the future,” Howlader said. “We will continue to monitor the mortality trends for lung cancer overall, and we hope to continue to see more positive results.”
For more information:
Nadia Howlader, PhD, can be reached at howladern@mail.nih.gov.
Perspective
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Charu Aggarwal, MD
Using SEER data, Howlader and colleagues reported on the effect of advances in lung cancer treatment on population mortality. They showed NSCLC mortality decreased by 6.3% among men annually between 2013 and 2016, with a decrease of about 3.1% between 2008 and 2016. Lung cancer survival increased from 26% among men diagnosed with NSCLC in 2001 to 35% among men diagnosed with NSCLC in 2014.
These results are remarkable, as they represent real evidence of a decline in lung cancer mortality. The rapid decline in NSCLC mortality between 2013 to 2016 is incredible and can be attributed in part to the availability of targeted therapies. Since 2016, a number of additional targeted agents have entered clinical trial development specifically for NSCLC, and several have received FDA approval.
In addition to EGFR and ALK, we now routinely test for ROS1 and RET fusions, MET exon 14 skipping mutations, BRAF mutations and NTRK rearrangements, with each subset associated with a highly effective targeted therapy. Drugs for targets such as HER2/Neu, EGFR exon 20 mutations and KRAS G12C are actively being tested, further increasing the reach of precision medicine and personalized therapy in NSCLC.
In the future, we expect to see further improvement in survival outcomes for patients with metastatic NSCLC, advances that are not just related to targeted therapy. Over the last 5 years, we have seen advances with immunotherapy for patients who do not harbor an actionable mutation.
For instance, at last year’s ASCO Annual Meeting, Garon and colleagues presented data showing that pembrolizumab (Keytruda, Merck) monotherapy provided durable activity and high rates of 5-year OS among both treatment-naive and previously treated patients with NSCLC, with a 5-year OS rate that exceeded 25%, the highest ever for patients with stage IV NSCLC without a driver mutation. Similar data have been presented with nivolumab (Opdivo, Bristol-Myers Squibb) and, in the near future, we expect to see updates of other trials with combination chemo-immunotherapy, as well as combination immunotherapy regimens as clinical trial data mature.
In summary, this is an encouraging report of a significant reduction in lung cancer mortality in the U.S. general population, and we anticipate further improvement in OS over the next few decades.
Reference:
Garon EB, et al. Abstract LBA9015. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
HemOnc Today Editorial Board Member
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