Immunotherapy or Chemoimmunotherapy in Older Adults With Advanced Non–Small Cell Lung Cancer

Abstract

ImportanceImmune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard treatment for non–small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy for patients 75 years and older.ObjectiveTo inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of ICI-chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC.Design, Setting, and ParticipantsThis retrospective cohort study included 58 centers in Japan. The cohort consisted of patients 75 years and older with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC. Patients started first-line systemic therapy between December 2018 and March 2021. Those receiving first-line molecular targeted drugs were excluded. The data were analyzed from February 2022 to October 2022.ExposuresSystemic therapy.Main Outcomes and MeasuresThe main outcomes were overall survival (OS), progression-free survival (PFS), and safety.ResultsA total of 1245 patients (median [range] age, 78 [75-95] years; 967 [78%] male) with NSCLC were included in the cohort. Programmed death ligand–1 (PD-L1) expression of less than 1% occurred in 268 tumors (22%); 1% to 49% in 387 tumors (31%); 50% and higher in 410 tumors (33%), and unknown expression in 180 tumors (14%). Median OS was 20.0 (95% CI, 17.1-23.6) months for the 354 patients receiving ICI-chemotherapy (28%); 19.8 (95% CI, 16.5-23.8) months for the 425 patients receiving ICI alone (34%); 12.8 (95% CI, 10.7-15.6) months for the 311 patients receiving platinum-doublet chemotherapy (25%); and 9.5 (95% CI, 7.4-13.4) months for the 155 patients receiving single-agent chemotherapy (12%). After propensity score matching, no differences in OS and PFS were found between the patients receiving ICI-chemotherapy vs ICI alone. Each group consisted of 118 patients. For PD-L1 expression of 1% and higher the OS hazard ratio (HR) was 0.98 (95% CI, 0.67-1.42; P = .90), and the PFS HR was 0.92 (95% CI, 0.67-1.25; P = .59). Significance was also not reached when separately analyzed for lower or higher PD-L1 expression (1%-49% or ≥50%). However, grade 3 or higher immune-related adverse events occurred in 86 patients (24.3%) treated with ICI-chemotherapy and 76 (17.9%) with ICI alone (P = .03).Conclusions and RelevanceIn this study, ICI-chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older. Based on these results, ICI alone may be recommended for older adult patients with PD-L1–positive NSCLC.

Real-World Prevalence and Tolerability of Immune-Related Adverse Events in Older Adults with Non-Small Cell Lung Cancer: A Multi-Institutional Retrospective Study

“…Immune checkpoint inhibitors (ICIs) have emerged as indispensable frontline therapies to manage advanced or recurrent NSCLCs without druggable mutations [ 4 ]. However, considering the age-associated immunosenescence, confirming ICI efficacy in elderly patients is necessary, and several studies have provided valuable insights [ 5 , 6 , 7 , 8 ]. Moreover, ICIs cause a unique array of adverse effects, termed immune-related adverse events (irAEs), wherein reinvigorated immune responses may inadvertently target healthy organs [ 9 ].…”

“…Morinaga et al conducted a real-world clinical study and observed that the irAE profile remained consistent across age groups [ 7 ]. However, Tsukita et al reported that combining ICI with chemotherapy in patients aged ≥75 years did not confer survival benefits and was associated with an increased incidence of grade ≥3 irAEs compared to ICI monotherapy [ 8 ]. Thus, information on irAEs in the elderly population remains unclear, and accumulating evidence in real-world clinical settings is necessary.…”