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

Alessio Cortellini, Maria G. Vitale, Federica De Galitiis, Francesca R. Di Pietro, Rossana Berardi, Mariangela Torniai, Michele De Tursi, Antonino Grassadonia, Pietro Di Marino, Daniele Santini, Tea Zeppola, Cecilia Anesi, Alain Gelibter, Mario Alberto Occhipinti, Andrea Botticelli, Paolo Marchetti, Francesca Rastelli, Federica Pergolesi, Marianna Tudini, Rosa Rita SilvaDomenico Mallardo, Vito Vanella, Corrado Ficorella, Giampiero Porzio, Paolo A. Ascierto

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number376
JournalJournal of Translational Medicine
Issue number1
Publication statusPublished - Nov 15 2019


  • Cancer
  • Fatigue
  • IL-6
  • Immune-related adverse events
  • Immunotherapy
  • PD-1/PD-L1 inhibitors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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