Predicting survival of NSCLC patients treated with immune checkpoint inhibitors: Impact and timing of immune-related adverse events and prior tyrosine kinase inhibitor therapy

Abstract

IntroductionImmune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.ObjectiveTo investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.MethodsA single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI therapy between 2014 and 2018. Survival analysis utilized overall survival (OS) and real-world progression free survival (rwPFS) outcomes. Model performance matrices for predicting 1-year OS and 6-month rwPFS using linear regression baseline, optimal, and machine learning modeling approaches.ResultsPatients experiencing an irAE were found to have a significantly longer OS and rwPFS compared to patients who did not (median OS 25.1 vs. 11.1 months; hazard ratio [HR] 0.51, confidence interval [CI] 0.39- 0.68, P-value <0.001, median rwPFS 5.7 months vs. 2.3; HR 0.52, CI 0.41- 0.66, P-value <0.001, respectively). Patients who received TKI therapy before initiation of ICI experienced significantly shorter OS than patients without prior TKI therapy (median OS 7.6 months vs. 18.5 months; P-value < 0.01). After adjusting for other variables, irAEs and prior TKI therapy significantly impacted OS and rwPFS. Lastly, the performances of models implementing logistic regression and machine learning approaches were comparable in predicting 1-year OS and 6-month rwPFS.ConclusionThe occurrence of irAEs, the timing of the events, and prior TKI therapy were significant predictors of survival in NSCLC patients on ICI therapy. Therefore, our study supports future prospective studies to investigate the impact of irAEs, and sequence of therapy on the survival of NSCLC patients taking ICIs.

Association between immune-related adverse events and immunotherapy efficacy in non-small-cell lung cancer: a meta-analysis

“…Using the criteria outlined in the Methods section, 66 publications were evaluated by browsing the full set of studies; however, some did not provide sufficient outcome data from the two approaches. Finally, 54 articles ( Ahn et al, 2019 ; Akamatsu et al, 2020 ; Aso et al, 2020 ; Baldini et al, 2020 ; Berner et al, 2019 ; Bjørnhart et al, 2019 ; Bouhlel et al, 2020 ; Campredon et al, 2019 ; Cortellini et al, 2019 ; Chen et al, 2021 ; Chmielewska et al, 2021 ; Cui et al, 2020 ; Cortijo-Cascajares et al, 2023 ; Daniello et al, 2021 ; Dupont et al, 2019 ; Fujimoto et al, 2018 ; Fukihara et al, 2019 ; Grangeon et al, 2019 ; Guezour et al, 2022 ; Haratani et al, 2018 ; Imai et al, 2020 ; Isono et al, 2021 ; Kim et al, 2017 ; Kobayashi et al, 2020 ; Ksienski et al, 2019 ; Kubo et al, 2020 ; Lesueur et al, 2018 ; Lisberg et al, 2018 ; Morimoto et al, 2021 ; Naqash et al, 2020 ; Noguchi et al, 2020 ; Osorio et al, 2017 ; Owen et al, 2018 ; Park et al, 2021 ; Peiró et al, 2019 ; Ricciuti et al, 2019 ; Rose et al, 2021 ; Rubino et al, 2021 ; Sato et al, 2018 ; Sayer et al, 2023 ; Schweizer et al, 2020 ; Shukla et al, 2021 ; Sonehara et al, 2021 ; Socinski et al, 2023 ; Sugano et al, 2020 ; Suh et al, 2018 ; Tambo et al, 2020 ; Teraoka et al, 2017 ; Thuillier et al, 2021 ; Toi et al, 2018 ; Wang et al, 2022 ; Yamaguchi et al, 2020 ; Zhang et al, 2021 ; …”

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%.…”

“…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).…”

Clinical Features Associated with Immune Checkpoint Inhibitor Nephritis: A Single-Center Clinical Case Series

“…The role of continuing low-dose steroids (prednisone 10 mg or less) with re-challenge has been shown to be successful in patients' other immune adverse events such as ICI-related liver injury and may also be a potential strategy for reducing re-aggravation of renal injury in patients undergoing rechallenge [13]. Despite the break in treatment, signi cant overall survival and real-world progression-free survival bene ts were shown in lung cancer patients who developed an IRAE [14,15] Of the two patients (cases #3 and #6) who had concomitant proteinuria, the patient (case #3) with FSGS had subsequent resolution of proteinuria after receiving steroid therapy.…”