Efficacy and immune-related adverse event associations in avelumab-treated patients

Autor: Isabell Speit, Sandra P. D'Angelo, Karen Kelly, Marcis Bajars, Vijay Kasturi, Arun Rajan, Juliane Manitz, Manish R. Patel, James L. Gulley, Andrea B. Apolo, John Warth
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Adult
Male
Cancer Research
medicine.medical_specialty
Drug-Related Side Effects and Adverse Reactions
Immune checkpoint inhibitors
medicine.medical_treatment
Immunology
Improved survival
biostatistics
Antibodies
Monoclonal
Humanized
programmed cell death 1 receptor
Avelumab
03 medical and health sciences
Young Adult
0302 clinical medicine
Immune system
Antineoplastic Agents
Immunological
Internal medicine
medicine
Immunology and Allergy
Humans
Adverse effect
RC254-282
Aged
Pharmacology
Aged
80 and over
Clinical/Translational Cancer Immunotherapy
business.industry
Proportional hazards model
Confounding
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immunotherapy
Middle Aged
030104 developmental biology
030220 oncology & carcinogenesis
Molecular Medicine
Female
immunotherapy
business
medicine.drug
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 8, Iss 2 (2020)
Journal for Immunotherapy of Cancer
ISSN: 2051-1426
Popis: BackgroundAdverse events (AEs) of special interest that arise during treatment with immune checkpoint inhibitors, including immune-related AEs (irAEs), have been reported to be associated with improved clinical outcomes. We analyzed patients treated with avelumab from the JAVELIN Solid Tumor and Merkel 200 trials, examining the association between AEs and efficacy while adjusting for confounding factors such as treatment duration and event order.MethodsWe analyzed efficacy and safety data from 1783 patients treated with the programmed death ligand 1 inhibitor avelumab who were enrolled in expansion cohorts of the JAVELIN Solid Tumor and Merkel 200 trials. To analyze the association between irAEs and efficacy with regard to survival, we used a time-dependent Cox model with time-varying indicators for irAEs, as well as multistate models that accounted for competing risks and time inhomogeneity.Results295 patients (16.5%) experienced irAEs and 454 patients (25.5%) experienced infusion-related reactions. There was a reduced risk of death in patients who experienced irAEs compared with those who did not (HR 0.71, 95% CI 0.59 to 0.85) using the time-dependent Cox model. The multistate model did not suggest that the occurrence of irAEs could predict response; however, it predicted a higher chance of irAEs occurring after a response. No association was observed between response and infusion-related reactions.ConclusionsPatients who experience irAEs showed improved survival. Although irAEs are not predictors for response to immune checkpoint inhibitors, increased vigilance for irAEs is needed after treatment with avelumab.Trial registration numbersNCT01772004 and NCT02155647.
Databáze: OpenAIRE
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