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. 2024 Nov 27:15:1419544.
doi: 10.3389/fimmu.2024.1419544. eCollection 2024.

Checkpoint based immunotherapy in non-small cell lung cancer: a real-world retrospective study

Luigi Liguori  1   2 , Gabriele Giorgio  1 , Giovanna Polcaro  1 , Valentina Pagliara  1 , Domenico Malandrino  1 , Francesco Perri  3 , Marco Cascella  1 , Alessandro Ottaiano  4 , Valeria Conti  1 , Alberto Servetto  2 , Roberto Bianco  2 , Stefano Pepe  1 , Francesco Sabbatino  1
Affiliations

Checkpoint based immunotherapy in non-small cell lung cancer: a real-world retrospective study

Luigi Liguori et al. Front Immunol. .

Abstract

Introduction: Immune checkpoint inhibitor (ICI)-based immunotherapy targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has radically changed the management of many types of solid tumors including non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated that ICIs improve the survival and the quality of life of patients with advanced non oncogene NSCLC as compared to standard therapies. However, not all patients achieve a clinical benefit from this immunotherapeutic approach. As a result, real-word validation of the efficacy and safety of ICIs can be useful for defining potential predictive biomarkers as well as for overcoming limitations linked to clinical trial restrictions.

Methods: We retrospectively retrieved the clinical data of patients with advanced non oncogene NSCLC treated with ICIs (anti-PD-1 or anti-PD-L1) as single agent or in combination with chemotherapy at "San Giovanni di Dio e Ruggi D'Aragona" University Hospital from January 2016 to December 2023. Potential correlations between clinical-pathological characteristics and safety or survival outcomes were investigated employing the Fisher's exact test, Mann-Whitney U test, the Kruskal-Wallis method and log-rank test, as applicable. Multivariate survival analyses were performed using the Cox proportional hazards model.

Results: Clinical data of 129 patients were retrieved. At a median follow-up of 29.70 months, progression-free survival (PFS) and overall survival (OS) were 5.27 months and 8.43 months, respectively. At the multivariate analyses, smoking status, presence of bone metastases and the occurrence of immune-related adverse events (irAEs) were correlated with both PFS and OS. Moreover, patients treated with anti-PD-1-based therapy achieved an increased clinical benefit than those treated with anti-PD-L1.

Discussion: In this study we described our real-world experience of ICIs for the treatment of patients with advanced non oncogene NSCLC. A decreased OS in our study population was reported as compared to that of patients included in the clinical trials. Noteworthy, correlations between clinical-pathological characteristics and survival outcomes emerged. Nevertheless, the potential integration of clinical-pathological characteristics as predictive biomarkers in more accurate therapeutic algorithms as well as the underlying biological mechanisms should be further validated in ad hoc studies.

Keywords: ICI; NSCLC; PD-1; PD-L1; biomarker; immunotherapy; predictive; real-world.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
PFS and OS of advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. At a median follow-up of 15.00 months, median PFS and OS were 5.27 months (range, 0.30-93.23 months) (A) and 8.43 months (range, 0.30-93.23 months) (B), respectively. PFS and OS analysis was performed using the Kaplan-Meier method.
Figure 2
Figure 2
Correlation between age of the advanced non oncogene NSCLC patients and the chosen type of ICI-based immunotherapy. Older patients received more ICI as monotherapy (IT) than younger patients (A). The former received less frequently the combination of chemotherapy and mono (CT+IT) or double (CT+IT+IT) ICI. Older patients also received more frequently anti-PD-L1 therapy than anti-PD-1 therapy (B). Differences between groups were correlated by Kruskal-Wallis method. P <0.05 was considered statistically significant.
Figure 3
Figure 3
Association between smoking status and clinical outcomes in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based on smoking status. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 4
Figure 4
Association between concomitant administration of antidepressant and clinical outcomes in advanced NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based on concomitant administration of antidepressant. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 5
Figure 5
Association between concomitant administration of opioid and clinical outcomes in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based on concomitant administration of opioid. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 6
Figure 6
Association between ECOG PS and clinical outcomes in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based ECOG PS. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 7
Figure 7
Association between bone metastases and clinical outcomes in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based on the presence of bone metastases. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 8
Figure 8
Association between skin metastases and clinical outcomes in advanced oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based on the presence of skin metastases. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 9
Figure 9
Association between PD-L1 TPS and clinical outcomes in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based PD-L1 TPS. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 10
Figure 10
Association between PD-L1 TPS and clinical outcomes in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based on the absence (PD-L1 TPS < 1%) or the presence (PD-L1 TPS ≥ 1%) of PD-L1 TPS. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 11
Figure 11
Association between the occurrence of irAEs and clinical outcomes in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based on the presence or absence of irAEs. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 12
Figure 12
Association between grade 1-2 irAEs and clinical outcomes in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based on the occurrence of irAEs. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 13
Figure 13
Association between type of ICI-based immunotherapy and clinical outcomes in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. PFS (A) and OS (B) of advanced NSCLC patients treated with ICI-based immunotherapy were stratified based on type of ICIs. Specifically, anti-PD-1-based immunotherapy versus anti-PD-L1-based immunotherapy. PFS and OS were compared using the Kaplan-Meier method. Differences in patients’ survival were analyzed using a log-rang test. P <0.05 was considered statistically significant.
Figure 14
Figure 14
Multivariate analysis testing the correlation between clinical-pathological characteristics and PFS (A) or OS (B) in advanced non oncogene NSCLC patients treated with ICI-based immunotherapy. Multivariate survival analyses were performed using the Cox proportional hazards model. Symbols *,**,*** indicate P value < 0.05, 0.005, 0.001.
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