Treatment sequence after first-line immunotherapy in older adults with advanced NSCLC (NEJ057)

Optimal management of older patients with advanced non-small cell lung cancer (NSCLC) following progression on immune checkpoint inhibitors (ICIs) remains uncertain, as large-scale evidence guiding second-line therapy in this population is limited. Thus, we performed this study to evaluate transition rates and clinical outcomes of subsequent treatments in older patients with NSCLC after first-line ICI-based therapy.

This multicenter retrospective cohort study included 1245 patients aged ≥ 75 years with advanced or recurrent epidermal growth factor receptor mutation-negative and anaplastic lymphoma kinase rearrangements-negative NSCLC who received first-line systemic therapy between December 2018 and March 2021 at 58 institutions in Japan. Outcomes included transition rates to second- and third-line therapy, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).

Of all patients, 354 received ICI plus chemotherapy and 425 received ICI monotherapy. Disease progression occurred in 82% and 77% of patients, respectively. Second-line therapy (most commonly single-agent chemotherapy) was administered to 48% and 31%, respectively. Median PFS with single-agent chemotherapy was 3.7 months in both groups. Median OS was 9.5 and 9.9 months, respectively. ORRs were 11% and 13%, respectively. After progression, 35% and 32% of patients received third-line treatment, which demonstrated limited efficacy. In older patients with advanced NSCLC, transition to second-line therapy after first-line ICI-based treatment was limited. However, the efficacy of single-agent chemotherapy as second-line treatment was comparable to real-world outcomes reported prior to ICIs.

These findings underscore the importance of providing appropriate second-line treatment for older patients. REGISTRY AND REGISTRATION NO.

UMIN Clinical Trials Registry (UMIN000046700).