Immunotherapy phase I trials in patients Older than 70 years with advanced solid tumours

Herin, H.; Aspeslagh, Sandrine; Castañón, Eduardo; Dyevre, Valérie; Marabelle, Aurélien; Varga, Andréa; Vinay, S. P.; Michot, Jean‐Marie; Ribrag, Vincent; Gazzah, Anas; Bahleda, Rastilav; Mir, Olivier; Massard, Christophe; Hollebecque, Antoine; Soria, Jean Charles; Baldini, Capucine

doi:10.1016/j.ejca.2018.03.002

Cited by 26 publications

(15 citation statements)

References 36 publications

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“…These studies did not show age differences with regard to grade ≥3 toxicity and response rates, but a higher rate of early treatment discontinuation and grade I-II adverse events was observed in older patients, especially in patients with multiple comorbidities or a poor performance status at baseline [ 8 , 17 ]. In addition, an overview of previous phase I trials in melanoma showed an increased incidence of grade I-II adverse events in older patients [ 20 ], and this was recently confirmed in a large observational study in >600 older patients on anti-PD1 treatment [ 21 ].…”

Section: Discussionmentioning

confidence: 90%

Toxicity, Response and Survival in Older Patients with Metastatic Melanoma Treated with Checkpoint Inhibitors

Glas

Bastiaannet

Bos

et al. 2021

Cancers

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Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of “real-world” older patients with metastatic melanoma and to identify predictors of outcome. Methods: We included patients aged ≥65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models. Results: We included 2216 patients. Grade ≥3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ≥75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65–75 and ≥75, respectively, for anti-PD1 treatment) and did not decrease with age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity. Conclusion: Response rates and toxicity outcomes of checkpoint inhibitors did not change with increasing age or comorbidity. However, the impact of grade I-II toxicity on quality of life deserves further study as older patients discontinue treatment more frequently.

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Section: Discussionmentioning

confidence: 90%

Toxicity, Response and Survival in Older Patients with Metastatic Melanoma Treated with Checkpoint Inhibitors

Glas

Bastiaannet

Bos

et al. 2021

Cancers

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“…However, the difference was not statistically significant. Median time before the occurrence of a first event was shorter in older patients [39].…”

Section: Immune-related Adverse Events In Older Patientsmentioning

confidence: 99%

Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer

et al. 2019

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The number of older patients with cancer is increasing as a result of the ageing of Western societies. Immune checkpoint inhibitors have improved cancer treatment and are associated with lower rates of treatment-related toxicity compared with chemotherapy in the general population. Nonetheless, immune checkpoint inhibitors have potentially serious immune-related adverse events, which might have a greater impact on older and more vulnerable patients and potentially influence treatment efficacy and quality of life. Previous clinical trials have shown no major increase in immune-related adverse events; however, older patients are underrepresented and relatively healthy in these trials. Observational studies suggest that older and more vulnerable patients may be at a higher risk of immune-related adverse events and early treatment discontinuation. Geriatric assessment could help identify older patients who will benefit from immune checkpoint inhibitors.

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“…The multimorbid, frail nature of many elderly patients has been noted to be associated with an increased likelihood of developing irAEs. The cumulative incidence of grade I–II irAEs are higher in patients >70 than their younger case‐controls (72 vs 48%, n = 220, P < .05), although with similar rates of grade III/IV irAEs 117 . Real‐world experience across 106 elderly (average age 74.4 range 65–90) metastatic patients has shown frailty being the most predictive risk factor for development of an irAE (odds ratio 3.03, P = .006) 118…”

Section: Phenotypic Predictors Of Responsementioning

confidence: 83%

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

Navani

Graves

Westhuizen

2020

Brit J Clinical Pharma

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Immune checkpoint blockade has transformed outcomes across solid organ tumours. Monoclonal antibodies targeting the negative inhibitory cytotoxic T lymphocyte‐associated protein 4 and programmed‐death 1/programmed death‐ligand 1 axis can lead to deep and durable responses across several tumour streams in the advanced setting. This immunotherapy approach is increasingly used earlier in the treatment paradigm. A rapidly evolving regulatory, reimbursement and drug development landscape has accompanied this novel class of immunotherapy. Unfortunately, only a small proportion of patients respond meaningfully to these agents. Here we review how the underlying tumoural genomic, histological and immunological characteristics interact within various patient phenotypes, leading to variations in response to checkpoint blockade. Concurrently, we outline the clinical trial and real‐world evidence that allows for appropriate selection of agent, dose and schedule in solid organ malignancies. An exploration of current trends in basic and translational research in immune checkpoint blockade accompanies a commentary on future clinical directions for checkpoint blockade in oncology.

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Immunotherapy phase I trials in patients Older than 70 years with advanced solid tumours

Cited by 26 publications

References 36 publications

Toxicity, Response and Survival in Older Patients with Metastatic Melanoma Treated with Checkpoint Inhibitors

Toxicity, Response and Survival in Older Patients with Metastatic Melanoma Treated with Checkpoint Inhibitors

Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

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