Older and younger patients treated with immune checkpoint inhibitors have similar outcomes in real-life setting

Corbaux, Pauline; Maillet, Denis; Boespflug, Amélie; Locatelli-Sanchez, Myriam; Perier‐Muzet, Marie; Duruisseaux, M.; Kiakouama-Maleka, Lize; Dalle, Stéphane; Falandry, Claire; Péron, Julien

doi:10.1016/j.ejca.2019.08.027

Cited by 65 publications

(55 citation statements)

References 33 publications

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“…Corbaux and colleagues investigated survival analyses including 410 patients from three institutions who received ICIs for NSCLC and melanoma. 18 They performed univariate and…”

Section: Discussionmentioning

confidence: 99%

Anti–PD-1 Monotherapy for Advanced NSCLC Patients with Older Age or Those with Poor Performance Status

Matsubara¹,

Seto²,

Takamori³

et al. 2021

OTT

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Anti-programmed death 1 (PD-1) antibodies have emerged as frontline treatments for patients with advanced non-small cell lung cancer (NSCLC) on the basis of global Phase III trials. However, current data regarding responses to anti-PD-1 therapy in older patients with NSCLC or those with poor performance status (PS) are limited. Therefore, we examined the therapeutic effect of anti PD-1 antibody in these patients. Patients: We retrospectively examined consecutive patients treated with anti-PD-1 monotherapy (pembrolizumab or nivolumab) from January 2016 to September 2018. Results: We enrolled 125 patients (median age, 60 years), 80.8% of whom were men. Patients aged ≥75 years were considered older patients (n = 15), and those with PS 2-3 were regarded as having poor PS (n = 11). The objective response and disease control rates were 15.4% and 46.2%, respectively, in older patients and 9.1% and 27.3%, respectively, in those with poor PS. Progression-free survival (PFS) and overall survival (OS) did not significantly differ between older and younger patients. However, poor PS was significantly associated with poor survival. High programmed death ligand 1 (PD-L1) expression in tumor specimens (≥50%) was associated with favorable survival in the entire cohort as well as patients with poor PS. Safety analyses demonstrated no significant difference in the occurrence of any adverse event, including grade ≥3 adverse events, between patients with poor PS or older age and the remaining patients. Conclusion: Anti-PD-1 therapy had similar efficacy in older and younger patients with NSCLC, whereas survival was significantly worse in patients with poor PS. However, immune checkpoint inhibitors may be considered for patients with poor PS harboring positive PD-L1 expression.

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“…Corbaux and colleagues investigated survival analyses including 410 patients from three institutions who received ICIs for NSCLC and melanoma. 18 They performed univariate and…”

Section: Discussionmentioning

confidence: 99%

Anti–PD-1 Monotherapy for Advanced NSCLC Patients with Older Age or Those with Poor Performance Status

Matsubara¹,

Seto²,

Takamori³

et al. 2021

OTT

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“…These significant differences in treatment between the cohorts might be of importance in weighing the impact of treatment on toxicity and survival. In recent years, retrospective, observational studies on safety and efficacy of treating patients with metastatic melanoma outside clinical trials [24][25][26][27][28][29]32] became increasingly available. In The Netherlands, treatment of patients with metastatic melanoma became centralized to fourteen expert hospitals who all register their data into the DMTR [31].…”

Section: Discussionmentioning

confidence: 99%

“…It has been postulated that immune checkpoint inhibitors may be less efficient in older patients because of the aging immune system leading to a wide range of alterations in immunity [21,22]. However, retrospective, observational studies and meta-analyses from clinical trials with older patients with metastatic melanoma, have shown that targeted therapies and immune checkpoint inhibitors show comparable safety and outcome as observed in the selected younger and healthier patients included in clinical trials [23][24][25][26][27][28][29]. In this study, we compare data on toxicity and outcomes (overall and melanoma specific survival) of patients with metastatic melanoma who received treatment in a population-based cohort of Dutch patients, stratified by age and BRAF status.…”

Section: Introductionmentioning

confidence: 99%

Outcomes for systemic therapy in older patients with metastatic melanoma: Results from the Dutch Melanoma Treatment Registry

Jochems

Bastiaannet

Aarts

et al. 2021

Journal of Geriatric Oncology

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Background: The incidence of metastatic melanoma is increasing in all ages. Multiple trials with targeted drugs and immune checkpoint inhibitors showed improved survival in metastatic melanoma. However, patients aged ≥75 years are often under-represented in clinical trials, therefore raising questions on safety and efficacy of treatment. Patients and methods: We analyzed a real-world cohort of 3054 patients with metastatic melanoma stratified for age (≤65 years, 66-74 years and ≥ 75 years), and BRAF status, providing data on treatment strategies, toxicity, and survival. Kaplan Meier curves and Cox Proportional Hazard Models were used to present overall survival (OS) and Melanoma Specific Survival (MSS). Results: Overall, 52.2% of patients were ≤ 65 years and 18.4% of patients ≥75 years. BRAF mutated tumors were found less often in patients ≥75 years: 34.5% versus 65% in patients ≤65 years. Patients ≥75 years received systemic therapy less frequently compared to their younger counterparts independent of the BRAF status. When receiving treatment, no statistical significant difference in grade 3 or 4 toxicity was observed. Three year Overall Survival rate was 13.7% (9.1-19.3) in patients ≥75 years versus 26.7% (23.1-30.4) in patients ≤65 years, with a Hazard Ratio (HR) of 1.71 (95%CI 1.50-1.95), p < 0.001. Three year Melanoma Specific Survival was 30.4% (22.0-39.2) versus 34.0% (29.7-38.2), HR 1.26 (95% CI 1.07-1.49), p = 0.005 with an adjusted HR of 1.21 (1.00-1.47), p = 0.049. Conclusion: Patients with metastatic melanoma ≥75 years are less frequently treated, but when treated there is no statistical significant increase in toxicity and only a borderline statistical significant difference in Melanoma Specific Survival was seen, compared to younger patients.

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“…Kugel et al found that responsiveness to anti-PD-1 was even enhanced in older human melanoma patients and aged mice, and this was associated with increased CD8 + T cell infiltration ( Kugel et al, 2018 ). Others have also found good ICB responsiveness in elderly patients with melanoma ( Ben-Betzalel et al, 2019 ; Betof et al, 2017 ) or non-small cell lung cancer ( Lichtenstein et al, 2019 ), and across multiple cancer types ( Corbaux et al, 2019 ). Overall, most human studies show at least similar efficacy of anti-CTLA-4 and anti-PD-(L)1 therapies in older compared to younger patients ( Huang et al, 2020 ; Pawelec, 2019 ; Poropatich et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

The effects of age and systemic metabolism on anti-tumor T cell responses

Drijvers

Sharpe

Haigis

2020

eLife

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Average age and obesity prevalence are increasing globally. Both aging and obesity are characterized by profound systemic metabolic and immunologic changes and are cancer risk factors. The mechanisms linking age and body weight to cancer are incompletely understood, but recent studies have provided evidence that the anti-tumor immune response is reduced in both conditions, while responsiveness to immune checkpoint blockade, a form of cancer immunotherapy, is paradoxically intact. Dietary restriction, which promotes health and lifespan, may enhance cancer immunity. These findings illustrate that the systemic context can impact anti-tumor immunity and immunotherapy responsiveness. Here, we review the current knowledge of how age and systemic metabolic state affect the anti-tumor immune response, with an emphasis on CD8+ T cells, which are key players in anti-tumor immunity. A better understanding of the underlying mechanisms may lead to novel therapies enhancing anti-tumor immunity in the context of aging or metabolic dysfunction.

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Older and younger patients treated with immune checkpoint inhibitors have similar outcomes in real-life setting

Cited by 65 publications

References 33 publications

Anti–PD-1 Monotherapy for Advanced NSCLC Patients with Older Age or Those with Poor Performance Status

Anti–PD-1 Monotherapy for Advanced NSCLC Patients with Older Age or Those with Poor Performance Status

Outcomes for systemic therapy in older patients with metastatic melanoma: Results from the Dutch Melanoma Treatment Registry

The effects of age and systemic metabolism on anti-tumor T cell responses

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