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The introduction of immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) in 2015 has resulted in meaningful survival gains for younger patients, but gains were far more modest among older patients, according to a large cohort study.

In advanced NSCLC patients under 55, median overall survival (OS) increased on the order of 4.5 months from 2011 to 2019, roughly 4 years following the first ICI approval in NSCLC. This improvement met the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) thresholds for a clinically meaningful benefit.

Yet over this same stretch, the median OS gain for patients 75 and older was a "less impressive" 1.1 months, thus failing to meet ASCO or ESMO's standards, reported Cary Gross, MD, of Yale School of Medicine in New Haven, Connecticut, and colleagues.

"Given that nearly half of newly diagnosed older patients were receiving ICIs by the end of the study period, this suggests that the substantial change in NSCLC treatment patterns has had minimal implications for the survival of older patients," the authors observed in . "In this population, the cost-effectiveness of ICIs may be overestimated."

Their cohort study included 53,719 adult NSCLC patients from predominantly community-based U.S. cancer clinics who had stage IIIB-IV disease diagnosed from 2011 to 2019, with follow-up through the end of 2020. A little more than half of the study participants were men, two-thirds were white, and the average age was 68.5 years.

Gross and his colleagues determined that the overall receipt of cancer-directed therapy increased from 69.0% in 2011 to 77.2% in 2019.

After the of an ICI for NSCLC, the use of ICIs increased from 4.7% in 2015 to 45.6% in 2019. On the other hand, the use of traditional chemotherapy as an initial treatment declined from 60.2% in 2011 to 22.8% in 2019. ICI use by 2019 was similar between the youngest and oldest patients (45.2% in those under 55 years vs 43.8% in patients 75 and older).

The predicted 2-year survival probability improvement from 2011 to 2018 was 7.1 percentage points higher for the younger group of patients (improving from 37.7% to 50.3% for those under 55) compared with the oldest patients in the study (from 30.6% to 36.2% for those age 75 and older).

Across age groups, the researchers found an inverse association between age group and median OS improvements from 2011 to 2019:

• <55 years: 4.5-month improvement in (11.5 to 16.0 months, respectively)
• 55-64 years: 2.1-month improvement (12.9 to 15.0 months)
• 65-74 years: 2.1 month improvement (11.2 to 13.3 months)
• ≥75 years: 1.1-month improvement (9.1 to 10.2 months)

ASCO frameworks for NSCLC trials define OS improvements of over 3.25 months for patients with non-squamous disease and of more than 2.5 months for those with squamous NSCLC as being clinically meaningful. Similarly, ESMO's Magnitude of Clinical Benefit Scale defines an OS increase of at least 3 months as being of substantial clinical benefit for cancers with a baseline survival of less than a year.

In a Marjory Charlot, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, and Jhanelle Gray, MD, of the Moffitt Cancer Center and Research Institute in Tampa, Florida, wrote that before drawing any conclusions about the association between age and survival, "it is important to note that there are several nuances in examining a clinically meaningful benefit with ICIs," including tumor histology, PD-L1 expression level, Eastern Cooperative Oncology Group status, and use of ICIs either alone or in combinations.

Nevertheless, Charlot and Gray said the study's results demonstrate the difficulty of interpreting and applying survival gains seen in clinical trials, since trial participants are usually younger and fitter. Still, the findings "may help inform shared decision-making discussions in clinical practice, particularly for the oldest adult age group with NSCLC," they suggested.

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