Immune-Related Adverse Events and Their Association With the Effectiveness of PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Real-World Study From China

Abstract

BackgroundProgrammed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors are increasingly used in China, but no real-world data are available about the immune-related adverse events (irAEs). This real-world retrospective study aimed to assess the safety and effectiveness of PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer (NSCLC) and to analyze the association between irAEs and effectiveness.MethodsThis was a retrospective study of the clinical data of patients with NSCLC treated with PD-1/PD-L1 inhibitors from August 2016 to November 2019 at Beijing Cancer Hospital. The patients were divided into the irAE or non-irAE groups. Overall adverse events, the impact of irAE on tumor response, and the association of irAEs with effectiveness were evaluated.ResultsOne hundred and ninety-one patients were included, including 70 (36.6%) patients in the irAE group and 121 (63.4%) patients in the non-irAE group. AE, grades 3–5 AEs, and irAE occurred in 107 (56.0%), 24 (12.6%), and 70 (36.6%) of the patients, respectively. The objective response rate (ORR) and disease control rate (DCR) were higher in the irAE group compared with the non-irAE group (42.0% vs. 25.8%, P=0.038; 91.9% vs. 70.8%, P=0.002). Multivariable analyses identified that irAE were associated with progression-free survival (HR=0.62, 95%CI: 0.43–0.91; P=0.015), but not with overall survival (HR=0.76, 95%CI: 0.44–1.28; P=0.299).ConclusionIn NSCLC treated with PD-1/PD-L1 inhibitors, patients with irAEs showed improved effectiveness over patients without irAEs. Future studies of anti-PD-1/PD-L1 immunotherapy should explore this association and the underlying biological mechanisms of efficacy.

Effectiveness and Safety of PD-1 Inhibitor Monotherapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer: A Real-World Exploratory Study

“…Of whom, the incidence of adverse reaction with grade ≥3 was only 16.2%, which indicated that the regimen of PD-1 inhibitor administration was acceptable and manageable. And the safety profile in our study was consistent with the adverse reactions of the previous retrospective study regarding PD-1 blockades in patients with advanced NSCLC [8]. However, some immunotherapyrelated adverse reactions should be paid more attention to the elderly patients who received PD-1 inhibitor monotherapy [37].…”

“…To our knowledge, the occurrence of NSCLC increased with age and previous work suggested that the onset age of the diagnosis of NSCLC in clinical practice was approximately 70 years old [7]. Additionally, regarding the epidemiological data in China, a previous real-world study demonstrated that the proportion of patients older than 65 years old was 35.1%, highlighting that the proportion of elderly cases (>65 years) among all NSCLC patients in China was over 35% [8]. Unfortunately, given that most clinical trials set strict age screening criteria (usually <75 years), the proportion of patients over the age of 75 who were able to participate in clinical trials was probably less than 10% [9], resulting in limited available evidence as clinical guidelines among elderly patients with NSCLC [10].…”

Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

“…Another clinically important and controversial issue is the relationship between irAE and patient survival (41). Earlier studies in melanoma and NSCLC had shown conflicting results, namely favorable (41)(42)(43)(44)(45) or indifferent outcome for patients developing irAEs (46)(47)(48), which was in part due to different handling of the "immortal-time bias" (ITB, aka A B FIGURE 4 | Progression-free and overall survival by occurrence of irAEs in a 14-week landmark analysis. (A) The median PFS under immunotherapy was 10 months (8.7-11.4) for patients without irAE vs. 17 months (10.3-23.6, logrank p = 0.003) for patients with irAEs in a 14-week landmark analysis.…”

“…Another clinically important and controversial issue is the relationship between irAE and patient survival ( 41 ). Earlier studies in melanoma and NSCLC had shown conflicting results, namely favorable ( 41 – 45 ) or indifferent outcome for patients developing irAEs ( 46 – 48 ), which was in part due to different handling of the “immortal-time bias” (ITB, aka “guaranteed-time bias”) by the various investigators ( 49 ). In a recent meta-analysis, both the confounding effect of the ITB and the real, positive association between irAE and patient survival that remains significant after control for ITB could be shown ( 50 ).…”

Comparative Safety of Immune Checkpoint Inhibitors and Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

“…Several studies have indicated that the development of irAEs after ICI treatment was associated with a better response and survival. [44,45] However, this association may be biased by differences in histological subtype, disease burden, and lines of treatment. We focused our analyses on TRAEs and irAEs with ICIs, providing detailed data for clinicians which will be helpful when choosing different treatment regimens with regards to both e cacy and safety.…”