# A Retrospective Study of First‐Line Immunotherapy for Advanced Non‐Small Cell Lung Cancer in the Elderly

## TL;DR

This study examines how effective and safe first-line immunotherapy is for elderly patients with advanced lung cancer, finding that age alone doesn't determine outcomes.

## Contribution

This is the first retrospective study comparing pembrolizumab plus chemotherapy versus tislelizumab plus chemotherapy in advanced NSCLC patients.

## Key findings

- Age is not a main prognostic factor for first-line immunotherapy effectiveness in advanced NSCLC.
- Non-smokers with no bone metastases and higher PNI had longer median overall survival.
- Pembrolizumab plus chemotherapy and tislelizumab plus chemotherapy showed no significant difference in efficacy or safety.

## Abstract

In this study, we compared the efficacy and safety of first‐line IO among different age subgroups of elderly patients, as well as in comparison to non‐elderly patients with advanced NSCLC. Additionally, we investigated hematological biomarkers associated with overall survival (OS) and compared the efficacy and safety of pembrolizumab plus chemotherapy (CT) versus tislelizumab plus CT in the treatment of advanced NSCLC.

We conducted a retrospective analysis of clinical data from 298 patients with stage IIIB–IVB NSCLC without driver mutations who received first‐line IO at The Second Xiangya Hospital of Central South University between June 1, 2019, and June 30, 2023. Differences between elderly and non‐elderly patients, as well as among different elderly age subgroups, were analyzed using the chi‐squared test and the Kruskal–Wallis H test. Receiver operating characteristic (ROC) curves were used to determine the optimal cut‐off values for hematological biomarkers. Patients were categorized into two groups based on treatment regimens: pembrolizumab plus CT and tislelizumab plus CT. To minimize baseline differences between the groups, 1:1 propensity score matching (PSM) was applied. A two‐sided p‐value of < 0.05 was considered statistically significant.

The study population was divided into two groups: elderly group (≥ 65 years old, n = 145 cases) and non‐elderly group (< 65 years old, n = 153 cases). The elderly group was further divided into three subgroups: 65–69 years old group (n = 78 cases), 70–74 years old group (n = 48 cases), and ≥ 75 years old group (n = 19 cases). Kaplan–Meier survival analysis using the log‐rank test revealed no statistically significant difference in OS among the age groups (p = 0.100). Multivariate COX regression analysis indicated that smoking history, bone metastasis, PD‐L1 tumor proportion score (TPS), and prognostic nutritional index (PNI) are independent prognostic factors for OS. Monocyte count (M), NLR, PLR, MLR, PIV, and SII were negatively correlated with OS, while PNI was positively associated with OS in patients with advanced NSCLC. Before PSM, the median OS (mOS) for patients receiving pembrolizumab plus CT and tislelizumab plus CT was 39.180 months (95% CI: 25.440–NA) and not reached (95% CI: 42.110–NA), respectively, with no statistically significant difference (p = 0.287). After PSM, the mOS was 46.150 months (95% CI: 17.550–NA) in the pembrolizumab plus CT group, while it remained not reached (95% CI: 20.550–NA) in the tislelizumab plus CT group, again show no statistically significant difference (p = 0.346).

Age may not be the main prognostic factor for the effectiveness of first‐line immunotherapy in patients with advanced NSCLC. Longer mOS was observed in patients who were non‐smokers, had no bone metastases, exhibited PD‐L1 TPS ≥ 50%, and had a higher prognostic nutritional index (PNI), regardless of age. Furthermore, the efficacy and safety profiles of pembrolizumab plus CT versus tislelizumab plus CT show no differences in the treatment of advanced NSCLC.

This is a retrospective study of the efficacy and safety of first‐line immunotherapy in elderly patients with advanced NSCLC. The hematologic prognostic markers of first‐line immunotherapy in advanced NSCLC patients, especially PNI, were investigated. This is the first retrospective study to evaluate the efficacy and safety of pembrolizumab plus CT versus tislelizumab plus CT in patients with advanced NSCLC.