Immune Checkpoint Inhibitors in Real‐World Treatment of Older Adults with Non–Small Cell Lung Cancer

Abstract

OBJECTIVE To evaluate the efficacy and toxicity of immune checkpoint inhibitors (ICIs) in older patients with advanced non–small cell lung cancer (NSCLC) seen in routine clinical practice. DESIGN Retrospective study. SETTING Single academic institution and its affiliated centers. PARTICIPANTS Patients 70 years or older with advanced‐stage NSCLC seen between April 1, 2015, and April 1, 2017, and treated with ICIs. MEASUREMENTS Efficacy data included overall survival (OS) and time to treatment failure (TTF), stratified by age, comorbidities (Charlson Comorbidity Index [CCI]), and Eastern Cooperative Oncology Group Performance Status (ECOG PS), and estimated using the Kaplan‐Meier method and log‐rank test. Toxicity data included immune‐related adverse events (irAEs), need for glucocorticoids, and hospitalization. The associations of toxicity with age, CCI, and ECOG PS were evaluated using the exact χ2 test or Fisher exact test. RESULTS We included 75 patients (median age: 74 y; range, 70‐92 y); 53% had a CCI of 3 or higher; 49% had ECOG PS of 2 or higher. Median OS for the whole cohort was 8.2 months (ECOG PS 0‐1 vs ≥2: 13.7 vs 3.8 mo; p < .01). Median TTF was 4.2 months (ECOG PS 0‐1 vs ≥2: 5.6 vs 2.0 mo; p = .02). Overall, 37% of patients experienced irAE of any grade (a total of 37 events); 8% were grade 3 or higher (no ICI‐related deaths). Of those who discontinued ICIs (N = 64), 15% were due to irAEs. Of those who experienced irAEs, 64% required glucocorticoids. Hospitalizations during ICI treatment occurred in 72%. Toxicity generally did not differ by age, CCI, or ECOG PS. CONCLUSIONS Outcomes in our cohort were driven by ECOG PS rather than chronological age or comorbidities. The relatively high rates of ICI discontinuation, use of glucocorticoids, and hospitalization during ICI treatment in our study highlight the vulnerability of older adults with advanced NSCLC even in the immunotherapy era. J Am Geriatr Soc 67:905–912, 2019.

Systemic therapy for elderly patients with non–small cell lung cancer: Where do we stand in 2019?

“…What other real-world evidence do we have to guide therapy for older individuals with mNSCLC?In a recent study by Muchnik et al in patients aged >70 years who were treated with immune checkpoint inhibitors, the ECOG PS, rather than chronological age or comorbidities, largely drove outcomes. 7 The population was similar to that of the SEER analysis reported by Youn et al 2 in this issue of Cancer in that the majority of the patients received nivolumab (87%) and received therapy in the second-line setting (69%). Similar to the SEER analysis, results from the study by Muchnik et al 7 demonstrated that older patients in general derived similar benefits from immune checkpoint inhibitors.…”

“…Conversely, among approximately one-half of the patients (49%) with an ECOG PS of ≥2, the median survival was a mere 3.8 months compared with 13.7 months in patients with an ECOG PS of 0 to 1. 7 The study by Youn et al 2…”

“…Similar to the SEER analysis, results from the study by Muchnik et al demonstrated that older patients in general derived similar benefits from immune checkpoint inhibitors. Conversely, among approximately one‐half of the patients (49%) with an ECOG PS of ≥2, the median survival was a mere 3.8 months compared with 13.7 months in patients with an ECOG PS of 0 to 1 . The study by Youn et al included relatively few patients with an ECOG PS ≥2 (11.5%) and therefore did not provide a large enough sample size with which to specifically address this question.…”

Initial Experience after Transition to Immune Checkpoint Inhibitors in Patients with Non-small Cell Lung Cancer Treated in a Rural Healthcare Region

“…Muchnik et al evaluated 75 patients who were 70 years or older with advanced-stage NSCLC treated with an ICI between 2015 and 2017 [17]. Of these, 49% had ECOG PS ≥2 disease.…”

Mechanisms of checkpoint inhibition-induced adverse events

“…Various clinical parameters have been considered to potentially predict CPI toxicity. Age in NSCLC does not appear to predict for increased risk of toxicity; however, older patients were more likely to require intervention to manage irAEs . A study investigating the impact of body composition parameters on ipilimumab toxicity found sarcopenia and low muscle attenuation to be significantly associated with high‐grade adverse events on multivariate analysis [odds ratio (OR) = 5·34 and 5·23, respectively] .…”