Study Shows Varied Immunotherapy Benefits Among Younger and Older Patients With NSCLC

The survival benefits of immune checkpoint inhibitors varied in young patients versus older patients with advanced non–small-cell lung cancer, a recent study found.

The treatment armamentarium for non–small-cell lung cancer (NSCLC) has expanded substantially in recent decades, including the addition of immune checkpoint inhibitors (ICIs), and a recent study showed that there has been quick uptake of ICIs across patient age groups. But the analysis, published in JAMA Oncology, also found that corresponding survival improvements varied by age group, with older patients seeing a less significant impact.

“Although these newer treatments have had comparable effectiveness between younger and older patients in clinical trials, such results may not be reflective of those in the community setting given that these patients tend to differ from those who participate in clinical trials,” the authors wrote.

Still, they noted that several studies have suggested the adoption of these novel therapeutics as possible contributors to the overall decrease in lung cancer mortality seen in recent years. Confounding factors such as the diagnosis of lung cancer in earlier stages could also contribute substantially to decreased mortality overall, however.

The current study aimed to assess the impact of the rapid uptake of ICIs across age groups by evaluating treatment and survival trends before and after the widespread availability of ICIs. Researchers also explored ICI use with and without chemotherapy, as some prior research has suggested that combination therapy including chemotherapy may be more effective than ICIs alone in some settings.

The retrospective, multicenter cohort study included a total of 53,719 patients diagnosed with advanced NSCLC between January 2011 and December 2019, and follow-up was through December 31, 2020. The aim was to compare outcomes before and after the initial FDA approval of ICIs in 2015.

The mean patient age was 68.5 years, and 61.9% of patients were diagnosed with stage IV NSCLC. A total of 39,272 patients (73.1%) in the overall cohort were treated for NSCLC.

In 2011, 69% of patients were receiving treatment, compared with 77.2% in 2019. ICIs were used as an initial treatment in 4.7% of cases in 2015 vs 45.6% in 2019. Traditional chemotherapy showed the opposite trend, declining from 60.2% to 22.8% in 2011 and 2019, respectively. The percentage of patients receiving tyrosine kinase inhibitors (TKIs) was 8.6% in 2011 and 8.9% in 2019. The increases in overall treatment rate and use of ICIs were similar regardless of age group.

Median overall survival (OS) was similar across age groups from 2011 to 2015. By 2019, median OS in patients aged 55 or younger had increased from 11.5 months (95% CI, 9.1-13) in 2011 to 16 months (95% CI, 13.6-19). Patients 55 to 64 years also saw an OS increase over time, with a median of 12.9 months (95% CI, 11.1-13.9) in 2011 to 15 months (95% CI, 13.7-17) in 2019. OS increased from 11.2 months (95% CI, 10.3-12.2) in 2011 to 13.3 months (95% CI, 9.6-11) in 2019 for patients 65 to 74 years. Patients 75 years or older saw a more modest increase from 9.1 months (95% CI, 8.4-9.9) in 2011 to 10.2 months (95% CI, 9.6-11) in 2019.

In patients younger than 55 years who were treated for NSCLC, median OS increased from 14.8 months (95% CI, 13-16.6 months) in 2015 to 19.0 months (lower 95% CI, 16.7 months; upper 95% CI, not estimated due to insufficient number of events) in 2019. But in patients 75 years or older, median OS increased from 12.3 months (95% CI, 11.1-13.3) in 2015 to 13 months (95% CI, 12.0-13.9) in 2019.

In patients younger than 55 years, the predicted probability of 2-year survival increased from 37.7% to 50.3% from 2011 to 2013 and 2017 to 2018, respectively. In patients 75 years or older, there was a smaller increase from 30.6% to 36.2% in the same time frame.

“Among younger patients, median survival increased on the order of 4 to 5 months,” the authors wrote. “This change meets the ASCO and ESMO threshold for a clinically meaningful benefit, suggesting that the adoption of ICIs has been associated with meaningful benefit for younger patients with NSCLC.” In older patients, however, the improvements were smaller and do not meet the criteria for a clinically meaningful survival benefit in the study cohort.

Previous studies deeming ICIs cost-effective have been based on survival data in trials, which may overestimate the benefit to older patients based on the current study’s findings, the authors noted. The study did not explore other meaningful outcomes such as treatment burden or quality of life improvements that could also be relevant and warrant analyzing, the authors added.

“In addition, the static pricing of cancer medications across ages, despite substantial variation in effectiveness by age group, means Medicare receives far less value with respect to survival benefit for its cancer treatment spending than it could under a value-based care model,” the authors wrote. “In this case, Medicare is likely paying for therapies that do not meet criteria for clinically meaningful survival benefits, while other outcomes remain unexplored. “


Voruganti T, Soulos PR, Mamtani R, Presley CJ, Gross CP. Association between age and survival trends in advanced non–small cell lung cancer after adoption of immunotherapy. JAMA Oncol. 2023;9(3):334-341. doi:10.1001/jamaoncol.2022.6901

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