Association Between Age and Survival Trends in Advanced Non–Small Cell Lung Cancer After Adoption of Immunotherapy

Abstract

ImportanceThe introduction of immune checkpoint inhibitors (ICIs) has transformed the care of advanced non–small cell lung cancer (NSCLC). Although clinical trials suggest substantial survival benefits, it is unclear how outcomes have changed in clinical practice.ObjectiveTo assess temporal trends in ICI use and survival among patients with advanced NSCLC across age strata.Design, Setting, and ParticipantsThis cohort study was performed in approximately 280 predominantly community-based US cancer clinics and included patients aged 18 years or older who had stage IIIB, IIIC, or IV NSCLC diagnosed between January 1, 2011, and December 31, 2019, with follow-up through December 31, 2020. Data were analyzed April 1, 2021, to October 19, 2022.Main Outcomes and MeasuresMedian overall survival and 2-year survival probability. The predicted probability of 2-year survival was calculated using a mixed-effects logit model adjusting for demographic and clinical characteristics.ResultsThe study sample included 53 719 patients (mean [SD] age, 68.5 [9.3] years; 28 374 men [52.8%]), the majority of whom were White individuals (36 316 [67.6%]). The overall receipt of cancer-directed therapy increased from 69.0% in 2011 to 77.2% in 2019. After the first US Food and Drug Administration approval of an ICI for NSCLC, the use of ICIs increased from 4.7% in 2015 to 45.6% in 2019 (P < .001). Use of ICIs in 2019 was similar between the youngest and oldest patients (aged <55 years, 45.2% vs aged ≥75 years, 43.8%; P = .59). From 2011 to 2018, the predicted probability of 2-year survival increased from 37.7% to 50.3% among patients younger than 55 years and from 30.6% to 36.2% in patients 75 years or older (P < .001). Similarly, median survival in patients younger than 55 years increased from 11.5 months to 16.0 months during the study period, while survival among patients 75 years or older increased from 9.1 months in 2011 to 10.2 months in 2019.Conclusions and RelevanceThis cohort study found that, among patients with advanced NSCLC, the uptake of ICIs after US Food and Drug Administration approval was rapid across all age groups. However, corresponding survival gains were modest, particularly in the oldest patients.

First-line Immunotherapy and Clinically Meaningful Survival Benefits for the Oldest Adults With Lung Cancer

“…Another important consideration that emerges from the findings of Voruganti et al 5 To our knowledge, this is the first report to assess clinically meaningful survival gains in the era of ICIs in advanced NSCLC across age strata using clinical practice data. The findings from Voruganti et al 5 may help inform shared decisionmaking discussions in clinical practice, particularly for the oldest adult age group with NSCLC.…”

“…Another important consideration that emerges from the findings of Voruganti et al 5 is how to interpret and apply the survival gains observed in clinical trials to clinical practice, particularly in shared decision-making discussions with adults in the oldest age groups. Clinical trial participants are typically Related article page 334 the fittest of the fit and are less likely to represent the general population of patients receiving cancer treatment in clinical practice.…”

“…These findings have relevant clinical implications given that the median age at lung cancer diagnosis is 71 years and that a clinically meaningful benefit, as defined by the American Society of Clinical Oncology, 6 is an overall survival gain of more than 3.25 and 2.5 months for squamous and nonsquamous NSCLC, respectively, which was not observed for the oldest age group. 5 Before drawing any definitive conclusions from these findings, it is important to note that there are several nuances in examining a clinically meaningful benefit with ICIs, including but not limited to tumor histology, PD-L1 expression level, Eastern Cooperative Oncology Group Performance Status, and use of ICIs either alone or in combination with a platinum doublet or other therapies. For example, in a recent pooled analysis of nivolumab and ipilimumab (both ICIs) in patients with squamous and nonsquamous NSCLC, all PD-L1 expression levels, and Eastern Cooperative Oncology Group Performance Status of 0 and 1, median OS was highest in the nonsquamous group (20 months) compared with the squamous group (15 months), with overall median OS in the age group 75 years and older being comparable to younger groups at 20 months.…”

“…In this issue of JAMA Oncology , Voruganti et al attempt to answer an important and clinically relevant question: are the survival gains from first-line ICI use in clinical trials observed in clinical practice across all age strata in patients with advanced NSCLC? To answer this question and assess temporal trends in median OS across age strata in the pre-ICI and post-ICI adoption era, the investigators conducted a multisite retrospective cohort study of more than 50 000 patients with advanced NSCLC diagnosed between January 1, 2011, and December 31, 2019.…”

Estimating Cancer Treatment Tolerability for Older Adults With Advanced Cancer—The Holy Grail

“…Understanding who will experience treatment-related side effects is incredibly important, as the number of new cancer drugs is rapidly increasing, with new approvals monthly. Overall survival benefits are improving, yet gains can be modest, particularly among older adults with cancer …”