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

被引:17
作者
Kelly, Karen [1 ]
Manitz, Juliane [2 ,3 ]
Patel, Manish R. [4 ]
D'Angelo, Sandra P. [5 ,6 ]
Apolo, Andrea B. [7 ]
Rajan, Arun [8 ]
Kasturi, Vijay [3 ,9 ]
Speit, Isabell [3 ]
Bajars, Marcis [2 ,3 ]
Warth, John [2 ,3 ]
Gulley, James L. [7 ]
机构
[1] Univ Calif Davis, Comprehens Canc Ctr, Dept Internal Med, Sacramento, CA 95817 USA
[2] EMD Serono Res & Dev Inst Inc, Billerica, MA USA
[3] Merck KGaA, Darmstadt, Germany
[4] Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA
[5] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA
[6] Weill Cornell Med Coll, New York, NY USA
[7] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA
[8] NCI, Thorac & Gastrointestinal Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA
[9] EMD Serono Inc, Rockland, MA USA
关键词
programmed cell death 1 receptor; immunotherapy; biostatistics; JAVELIN SOLID TUMOR; CHECKPOINT INHIBITORS; NIVOLUMAB; SURVIVAL; IMMUNOTHERAPY; VITILIGO; ANTIBODIES; CTLA4;
D O I
10.1136/jitc-2020-001427
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Adverse 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. Methods We 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. Results 295 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. Conclusions Patients 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.
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页数:8
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