<p>Correlation of Immune-Related Adverse Events and Effects of Pembrolizumab Monotherapy in Patients with Non-Small Cell Lung Cancer</p>

Abstract

Purpose The effects of immune checkpoint inhibitors have been reported to be linked with immune-related adverse events (irAEs). In patients with advanced non-small-cell lung cancer, who tested positive for programmed death-ligand 1 (PD-L1), pembrolizumab, an immune checkpoint inhibitor can be used as a treatment, and it was found to improve overall survival. However, there are only a few reports on the relationship between the therapeutic effects of pembrolizumab in patients with lung cancer and the irAEs of pembrolizumab. The purpose of this study was to determine the correlation between immune-related adverse events and the effects of pembrolizumab monotherapy in patients with non-small-cell lung cancer. Patients and Methods From February 2017 to August 2019, we conducted a retrospective analysis of the effects of pembrolizumab treatment and immune-related adverse events in 94 patients with non-small-cell lung cancer treated with pembrolizumab only. Results In 63 cases, irAEs were observed. The most common irAE was rash. PD-L1 positivity ≥ 50% tended to cause irAEs. The median progression-free survival (PFS) rates with and without irAEs were 371 days (95% CI, 184-NR) and 67 days (95% CI, 51–87 days), respectively. In a multivariate analysis, irAEs and Eastern Cooperative Oncology Group performance status (PS) were the factors related to PFS. Conclusion In patients with lung cancer, who were treated with pembrolizumab monotherapy, the development of irAEs was likely indicative of the positive effects of pembrolizumab. This novel finding appears to be useful for clinicians who work with pembrolizumab for lung cancer treatment.

Correlation between immune-related adverse events and the efficacy of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: systematic review and meta-analysis

“…A total of 20 studies assessed HRs of PFS in the meta-analysis [ 6 , 13 – 19 , 21 – 27 , 30 – 34 ]. The results showed that PFS was significantly improved for the occurrence of irAEs compared with non-irAEs (HR = 0.55, 95% CI = 0.51–0.60, p < 0.001; shown in Fig.…”

Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non–Small Cell Lung Cancer

“…Patients who discontinue ICI treatment due to irAEs have continued to experience treatment benefit, suggesting a potentially mechanistic association between irAEs and ICI efficacy, even with relatively short exposure . Exploratory, retrospective analyses of studies with anti–programmed cell death 1 (PD-1) agents nivolumab and pembrolizumab in NSCLC showed longer progression-free survival (PFS) among patients who experienced irAEs than in those who did not, and other ICI studies showed that overall survival (OS) was longer in patients with irAEs than in those without . Further evaluation of irAE occurrence as a predictive clinical biomarker for ICI response in NSCLC is warranted.…”

Immune-Related Adverse Events and Survival Among Patients With Metastatic NSCLC Treated With Immune Checkpoint Inhibitors

“…The incidence of reported irAEs in NSCLC varies widely, ranging from 24.0% to 70.5%. This reflects heterogeneity including in study setting (observational vs randomized clinical trial), patient characteristics (cancer stage, PD-L1 status, geographical location, race and ethnicity), treatment parameters (ICI agent used either alone or combined with chemotherapy, treatment line), and irAE grading . In our cohort, the incidence of clinically meaningful irAEs was 37.0%.…”

“…Demographic characteristics (age, sex, race, body mass index, and ECOG), concomitant medications (corticosteroids, proton pump inhibitors, and antibiotics), peripheral laboratory markers (hemoglobin, albumin, C-reactive protein, and others), tumor characteristics (histology, stage, PD-L1 expression, driver mutation status, and disease burden), and treatment-related factors (treatment line, response, ICI agent, concurrent chemotherapy, time to starting ICI, cumulative dose, and cumulative cycles of ICI) are inconsistently reported as predictive factors associated with irAE development. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]48,[60][61][62] In our cohort, we identified several baseline patient characteristics associated with irAE development: 60 years or older, ECOG performance status 0, high expression of PD-L1, absence of bone metastases, DNLR of 3 or less, and levels of hemoglobin, albumin, and LDH within reference range. Other than response to ICI therapy, irAE development was not associated with treatment-related characteristics (ICI agent, ICI alone or in combination with chemotherapy, and treatment line) in our study population.…”

“…It is well established that although ICIs improve clinical outcomes in NSCLC, they are complicated by immune-related adverse events (irAEs), the incidence of which varies by study setting, patient selection, treatment parameters, and irAE grading . There is growing recognition across solid malignant neoplasms that irAEs affect overall survival (OS).…”