Association Between Immune-related Adverse Events and Efficacy of Immune Checkpoint Inhibitors in Non–small-cell Lung Cancer

Grangeon, M.; Tomasini, Pascale; Chaléat, S.; Jeanson, Arnaud; Souquet-Bressand, M.; Khobta, Nataliya; Bermudez, Julien; Trigui, Y.; Greillier, L.; Blanchon, Marilyne; Boucékine, Mohamed; Mascaux, Céline; Barlési, Fabrice

doi:10.1016/j.cllc.2018.10.002

Cited by 162 publications

(138 citation statements)

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“…The results of this study showed a significant association between the incidence of irAEs and higher ORR (22.9% vs. 5.7%, p<0.0001), DCR (72.4% vs. 36.7% p<0.001) as well as longer PFS (HR=0.42, p<0.001) and OS (HR=0.29, p<0.001) (37). The study confirmed a significant association of irAE in a form of hypothyroidism with longer PFS (HR=0.56, p=0.005) and OS (HR=0.46, p=0.01) and did not show significant differences according to the grade of irAEs (37). The association of immune-related thyroid dysfunction with effect of ICIs has been observed also in two other studies by Osorio et al (38) and Toi et al (39).…”

Section: Iraes and Outcome In Nsclcmentioning

confidence: 55%

“…The association of the incidence of irAEs with the effect of anti-PD1 (nivolumab, pembrolizumab) and anti-PD-L1 (atezolizumab) inhibitors in patients with advanced NSCLC (n=270) was recently confirmed by a retrospective study by conducted by Grangeon et al (37). The results of this study showed a significant association between the incidence of irAEs and higher ORR (22.9% vs. 5.7%, p<0.0001), DCR (72.4% vs. 36.7% p<0.001) as well as longer PFS (HR=0.42, p<0.001) and OS (HR=0.29, p<0.001) (37). The study confirmed a significant association of irAE in a form of hypothyroidism with longer PFS (HR=0.56, p=0.005) and OS (HR=0.46, p=0.01) and did not show significant differences according to the grade of irAEs (37).…”

Section: Iraes and Outcome In Nsclcmentioning

confidence: 80%

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Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

et al. 2020

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Section: Iraes and Outcome In Nsclcmentioning

confidence: 55%

Section: Iraes and Outcome In Nsclcmentioning

confidence: 80%

Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

et al. 2020

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“…25 In our study, OS, PFS and ORR were consistently found to be superior in patients who experienced cutaneous irAEs or rash. Endocrine irAEs, all analyzed together or by taking into account single immune-related thyroid dysfunctions, have also been reported to be a favorable prognostic indicator, 9,11,20,22,24,26 with only one exception. 25 In our study, endocrine irAEs were significantly associated with OS, PFS and ORR, even though only 7.1% of our patients experienced such irAEs, compared to approximately 10-15% in the literature.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with melanoma, 1-year OS and PFS were 49% [95%, CI 40-58] and 26% [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34], respectively (Supplementary Table 1). Median OS and PFS were 11.6 (iqr 3.4-29.6) and 3.9 (2.2-12.6) months, respectively.…”

Section: Efficacymentioning

confidence: 99%

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The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non–small-cell lung cancer: a real-life retrospective study

et al. 2019

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Background: Nivolumab and pembrolizumab, two PD1 inhibitors, trigger immune-related adverse events in approximately 50% of patients. Our objective was to determine whether these immunerelated adverse events are associated with patient outcomes. Patients and Methods: Retrospective cohort study, realized at the Institut Universitaire du Cancer de Toulouse, of all the patients treated with nivolumab or pembrolizumab off clinical trials. We included patients (i) diagnosed with unresectable stage III or stage IV melanoma or with recurrent stage IIIB or stage IV non-small cell lung cancer (ii) on nivolumab 3mg/kg or pembrolizumab 2mg/kg every 2 or 3 weeks respectively. Results: Of the 311 patients included (of 641 eligible subjects), 120 (38.6%) had melanoma and 191 (61.4%) had non-small cell lung cancer; 241 (77.5%) were treated with nivolumab with a median followup of 24 months (20-29). We observed 166 immune-related adverse events in 116 (37.3%) patients, categorized as "early" (onset before 12 weeks in melanoma and before 8 weeks in lung cancer) in 63 (54.3%) patients. Early and late adverse events were significantly associated with an increase in overall survival: adjusted hazard ratio 0.58 [0.41-0.84] (p = .003) and 0.28 [0.16-0.50] (p < .001) respectively. The overall response rate was significantly increased in patients with an immune-related adverse event (53.9% vs 12.9%, p < .001) Conclusions: This study validates the association between immune-related adverse events and anti-PD1 efficacy in real-life, especially if these events are delayed. Our results, along with further studies on the place of immunosuppressive drugs in the therapeutic strategy, could improve the management of these adverse events.

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

Cook,

Samuel,

Meyers

et al. 2024

JAMA Netw Open

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ImportanceImmune-related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) therapy reportedly improve overall survival (OS) in patients with non–small cell lung cancer (NSCLC). However, studies have been small and the association between irAE severity and OS remains poorly defined.ObjectiveTo examine the association between irAEs and their severity with OS in patients with locally advanced or metastatic NSCLC receiving ICIs.Design, Setting, and ParticipantsThis retrospective observational cohort study included patients with NSCLC receiving ICIs between March 1, 2014, and November 30, 2021, with follow-up until March 31, 2023. Data analysis was completed April 26, 2023. The Alberta Immunotherapy Database, a provincial, multicenter cohort, was used to capture data from patients receiving ICIs in Alberta, Canada. Participants included 803 patients 18 years or older who received at least 1 cycle of ICI (alone or with chemotherapy), agnostic to treatment line.ExposureDeveloping an irAE mandating delay or discontinuation of ICI therapy and/or systematic corticosteroids for management of toxic effects (hereinafter referred to as clinically meaningful irAEs).Main Outcomes and MeasuresThe primary outcome was association between irAEs and OS according to Kaplan-Meier analysis. Clinically meaningful irAEs were identified. Patients with poor prognosis (survival &lt;3 months) who may have died prior to irAE development were excluded from OS analysis, mitigating immortal time bias. Adjusted Cox proportional hazards regression analyses ascertained variables associated with OS.ResultsAmong the 803 patients included in the analysis, the median age of patients with irAEs was 69.7 (IQR, 63.1-75.2) years and the median age of those without irAEs was 67.5 (IQR, 60.4-73.3) years, with comparable sex distribution (139 of 295 men [47.1%] and 156 of 295 women [52.9%] with irAEs vs 254 of 505 men [50.3%] and 251 of 505 women [49.7%] without irAEs). Mitigating immortal time bias (n = 611), irAEs were associated with OS (median OS with irAEs, 23.7 [95% CI, 19.3-29.1] months; median OS without irAEs, 9.8 [95% CI, 8.7-11.4] months; P &lt; .001). No OS difference was associated with treatment in hospital vs as outpatients for an irAE (median OS, 20.8 [95% CI, 11.7-30.6] vs 25.6 [95% CI, 20.1-29.8] months; P = .33). Developing irAEs remained associated with OS in the total cohort after Cox proportional hazards regression with known prognostic characteristics (hazard ratio, 0.53 [95% CI, 0.40-0.70]; P &lt; .001).Conclusions and RelevanceIn this cohort study of 803 patients with locally advanced or metastatic NSCLC receiving ICIs, developing a clinically meaningful irAE was associated with improved OS. This association was not compromised by hospitalization for severe toxic effects. Whether and how ICI therapy resumption after an irAE is associated with OS warrants further study.

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Association Between Immune-related Adverse Events and Efficacy of Immune Checkpoint Inhibitors in Non–small-cell Lung Cancer

Cited by 162 publications

References 23 publications

Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non–small-cell lung cancer: a real-life retrospective study

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

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