Impact of Age on Outcomes with Immunotherapy in Patients with Non–Small Cell Lung Cancer

Abstract

Introduction: Immunotherapy has revolutionized the treatment of NSCLC, but little is known about the activity of programmed cell death 1 and programmed death ligand 1 blockade across age groups. Methods: We retrospectively evaluated patients with NSCLC who initiated programmed cell death 1 and programmed death ligand 1 inhibitors from January 2013 through July 2017. Medical records and radiographic imaging were reviewed to determine progression-free survival (PFS) and overall survival (OS). We also compared immunotherapy-related toxicities, steroid use, and hospitalizations by age. Results: Of the 245 patients, 26.1% were younger than 60 years, 31.4% were age 60 to 69 years, 31.0% were age 70 to 79 years, and 11.4% were age 80 years or older. The median PFS times by age group were as follows: younger than 60 years, 1.81 months; age 60 to 69 years, 2.53 months; age 70 to 79 years, 3.75 months; and age 80 years or older, 1.64 months (log-rank p value ¼ 0.055). The median OS times by age group were as follows: younger than 60 years, 13.01 months; age 60 to 69 years, 14.56 months; age 70 to 79 years, 12.92 months; and age 80 years or older, 3.62 months (log-rank p value ¼ 0.011). Rates of immunotherapy-related toxicities, steroid use, and hospitalizations did not differ by age. Conclusions: Although the OS and PFS benefits of immunotherapy differ by age, the rates of toxicity are similar regardless of age.

Clinical Efficacy of Immune Checkpoint Inhibitors in Older Non-small-Cell Lung Cancer Patients: A Meta-Analysis

“…Wu et al found older (≥65 years) patient derived better benefits than younger (<65 years) patients from the use of ICIs (10). However, patients more than 80 years old were reported to have shorter PFS compared with other age groups (11).…”

The effects of age and systemic metabolism on anti-tumor T cell responses

“…Kugel et al found that responsiveness to anti-PD-1 was even enhanced in older human melanoma patients and aged mice, and this was associated with increased CD8 + T cell infiltration ( Kugel et al, 2018 ). Others have also found good ICB responsiveness in elderly patients with melanoma ( Ben-Betzalel et al, 2019 ; Betof et al, 2017 ) or non-small cell lung cancer ( Lichtenstein et al, 2019 ), and across multiple cancer types ( Corbaux et al, 2019 ). Overall, most human studies show at least similar efficacy of anti-CTLA-4 and anti-PD-(L)1 therapies in older compared to younger patients ( Huang et al, 2020 ; Pawelec, 2019 ; Poropatich et al, 2017 ).…”

Real life safety and effectiveness of nivolumab in older patients with non-small cell lung cancer: Results from the Belgian compassionate use program

“…Real-life data, such as our own retrospective analysis, may help to increase the knowledge of ICIs effectiveness in older patients with NSCLC. In different retrospective studies [14][15][16][17][18][19], older and younger patients had similar effectiveness, although the results in the 'oldest old' remain rather conflicting. Lichtenstein et al reported similar median PFS but significant lower median OS in patients 80 years or older (OS 3.6 months versus 12.9 months in patients age 70-79 years, 14.6 months in patients aged 60-69 years and 13 months in patients younger than 60 years; p = 0.011) [19].…”

“…In different retrospective studies [14][15][16][17][18][19], older and younger patients had similar effectiveness, although the results in the 'oldest old' remain rather conflicting. Lichtenstein et al reported similar median PFS but significant lower median OS in patients 80 years or older (OS 3.6 months versus 12.9 months in patients age 70-79 years, 14.6 months in patients aged 60-69 years and 13 months in patients younger than 60 years; p = 0.011) [19]. Multivariate Cox regression, adjusted for baseline characteristics such as ECOG-PS and comorbidity, demonstrated in this study that patients age 80 years or older had a significant higher hazard for death compared with younger patients (HR 2.74; p = 0.002) [19].…”