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. 2019 Nov 15;17(1):376.
doi: 10.1186/s12967-019-02132-x.

Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice

Alessio Cortellini  1   2 , Maria G Vitale  3 , Federica De Galitiis  4 , Francesca R Di Pietro  5 , Rossana Berardi  6 , Mariangela Torniai  6 , Michele De Tursi  7 , Antonino Grassadonia  7 , Pietro Di Marino  8 , Daniele Santini  9 , Tea Zeppola  9 , Cecilia Anesi  9 , Alain Gelibter  10 , Mario Alberto Occhipinti  10 , Andrea Botticelli  5   10 , Paolo Marchetti  5   10 , Francesca Rastelli  11 , Federica Pergolesi  11 , Marianna Tudini  12 , Rosa Rita Silva  12 , Domenico Mallardo  13 , Vito Vanella  13 , Corrado Ficorella  14   15 , Giampiero Porzio  14   15 , Paolo A Ascierto  13
Affiliations

Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice

Alessio Cortellini et al. J Transl Med. .

Abstract

Background: Fatigue was reported as the most common any-grade adverse event (18.3%), and the most common grade 3 or higher immune-related adverse event (irAE) (0.89%) in patients receiving PD-1/PD-L1 checkpoint inhibitors in clinical trial.

Methods: The aim of this retrospective multicenter study was to evaluate the correlations between "early ir-fatigue", "delayed ir-fatigue", and clinical outcomes in cancer patients receiving PD-1/PD-L1 inhibitors in clinical practice.

Results: 517 patients were evaluated. After the 12-weeks landmark selection, 386 (74.7%) patients were eligible for the clinical outcomes analysis. 40.4% were NSCLC, 42.2% were melanoma, 15.3% renal cell carcinoma and 2.1% other malignancies. 76 patients (19.7%) experienced early ir-fatigue (within 1 month from treatment commencement), while 150 patients (38.9%) experienced delayed ir-fatigue. Early ir-fatigue was significantly related to shortened PFS (HR = 2.29 [95% CI 1.62-3.22], p < 0.0001) and OS (HR = 2.32 [95% CI 1.59-3.38], p < 0.0001) at the multivariate analysis. On the other hand, we found a significant association between the occurrence of early ir-fatigue, ECOG-PS ≥ 2 (p < 0.0001), and disease burden (p = 0.0003). Delayed ir-fatigue was not significantly related to PFS nor OS.

Conclusions: Early ir-fatigue seems to be negative prognostic parameter, but to proper weight its role we must to consider the predominant role of performance status, which was related to early ir-fatigue in the study population.

Keywords: Cancer; Fatigue; IL-6; Immune-related adverse events; Immunotherapy; PD-1/PD-L1 inhibitors.

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Conflict of interest statement

Dr Alessio Cortellini received speaker fees and grant consultancies by Astrazeneca, MSD, BMS, Roche, Novartis, Istituto Gentili, Astellas and Ipsen. Dr Maria G Vitale received speaker fees and grant consultancies by BMS, Ipsen, Novartis and Pfizer, Jansen, Astellas and Pierre Fabre.

Figures

Fig. 1
Fig. 1
Kaplan–Meier survival curves according to early ir-fatigue. a Progression free survival. b Overall survival
See this image and copyright information in PMC

References

    1. Abbas AK, Lohr J, Knoechel B, et al. T cell tolerance and autoimmunity. Autoimmun Rev. 2004;3(7–8):471–475. doi: 10.1016/j.autrev.2004.07.004. - DOI - PubMed
    1. Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008;224:166–182. doi: 10.1111/j.1600-065X.2008.00662.x. - DOI - PubMed
    1. Wang Y, Zhou S, Yang F, et al. Treatment-related adverse events of PD-1 and PD-L1 inhibitors in clinical trials: a systematic review and meta-analysis. JAMA Oncol. 2019 doi: 10.1001/jamaoncol.2019.0393. - DOI - PMC - PubMed
    1. Petrelli F, Grizzi G, Ghidini M, et al. Immune-related adverse events and survival in solid tumors treated with immune checkpoint inhibitors: a systematic review and meta-analysis. J Immunother. 2019 doi: 10.1097/CJI.0000000000000300. - DOI - PubMed
    1. Cortellini A, Chiari R, Ricciuti B, et al. Correlations between the immune-related adverse events spectrum and efficacy of anti-PD1 immunotherapy in NSCLC patients. Clin Lung Cancer. 2019;20(4):237–247.e1. doi: 10.1016/j.cllc.2019.02.006. - DOI - PubMed

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