Outcomes of chemotherapy with or without immunotherapy in older patients with non-small cell lung cancer and low PD-L1 expression

Background: Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have demonstrated efficacy in the treatment of non-small cell lung cancer (NSCLC) with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1–49%. However, older patients remain underrepresented in clinical trials, and optimal treatment strategies for this population remain unclear. This study sought to evaluate the efficacy and safety of first-line treatment with either platinum-based chemotherapy alone (Chemo) or in combination with ICIs (ICI/Chemo) in older patients with NSCLC who have low PD-L1 expression. Methods: This retrospective multicenter study included patients diagnosed with advanced NSCLC (stage IIIB–IV) with a PD-L1 TPS of 1–49% from 19 Japanese institutions. We examined the relationship between baseline patient characteristics and treatment outcomes within each group. Propensity score matching (PSM) was used to balance patient characteristics between the ICI/Chemo and Chemo groups.Results: We evaluated data from 613 patients, finding that the ICI/Chemo group (n=370) exhibited significantly longer median progression-free survival (PFS) and overall survival (OS) compared to the Chemo group (n=243). Among the 613 patients, 152 were aged ≥75 years. Of these, 63 received Chemo, while 89 underwent ICI/Chemo as first-line treatment. In this older cohort, ICI/Chemo significantly improved median PFS; however, no significant difference was observed in OS. Nonetheless, the incidence of grade ≥3 adverse events and pneumonitis of any grade was higher in the ICI/Chemo group compared to the Chemo group among older patients. Multivariate analysis using Cox proportional hazards models indicated that Eastern Cooperative Oncology Group performance status (ECOG PS) was significantly associated with PFS and OS. In older patients with ECOG PS 0, ICI/Chemo showed significant PFS benefits; in those with ECOG PS 1, both the PFS and OS were similar between the two groups. Conclusions: ICI combined with chemotherapy may be a potentially effective treatment strategy for older patients with NSCLC and low PD-L1 expression. However, compared with the overall population, the benefits of adding ICI to chemotherapy were decreased, while the risk of toxicity may increase, making appropriate patient selection crucial for this population. Particularly, in patients with ECOG PS 1, the additional benefit of ICI over chemotherapy was minimal in terms of efficacy, suggesting that the introduction of ICI combined with chemotherapy should be carefully considered for this patient population.