Assessing the impact of organ-specific lesion dynamics on survival in patients with recurrent urothelial carcinoma treated with atezolizumab or chemotherapy

ESMO Open

article

M. Kerioui¹  S. Desmée²  F. Mercier⁵  A. Lin⁶  B. Wu⁶  J.Y. Jin⁶  X. Shen⁷  C. Le Tourneau⁸  R. Bruno⁴  J. Guedj¹ 

[1] Université de Paris;Université de Tours, Université de Nantes;Institut Roche;Clinical Pharmacology;F. Hoffmann-La Roche AG;Clinical Pharmacology, Genentech Inc.;Product Development, Genentech Inc.;Department of Drug Development and Innovation ,(D3i), INSERM U900 Research Unit, Paris-Saclay University

关键词: cancer clinical trials;    nonlinear mixed-effects model;    survival prediction;    joint model;    immunotherapy;   

DOI  :  10.1016/j.esmoop.2021.100346

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Tumor dynamics typically rely on the sum of the longest diameters (SLD) of target lesions, and ignore heterogeneity in individual lesion dynamics located in different organs.Patients and methods Here we evaluated the benefit of analyzing lesion dynamics in different organs to predict survival in 900 patients with metastatic urothelial carcinoma treated with atezolizumab or chemotherapy (IMvigor211 trial).Results Lesion dynamics varied largely across organs, with lymph nodes and lung lesions showing on average a better response to both treatments than those located in the liver and locoregionally. A benefit of atezolizumab was observed on lung and liver lesion dynamics that was attributed to a longer duration of treatment effect as compared to chemotherapy (P value = 0.043 and 0.001, respectively). The impact of lesion dynamics on survival, assessed by a joint model, varied greatly across organs, irrespective of treatment. Liver and locoregional lesion dynamics had a large impact on survival, with an increase of 10 mm of the lesion size increasing the instantaneous risk of death by 12% and 10%, respectively. In comparison, lymph nodes and lung lesions had a lower impact, with a 10-mm increase in the lesion size increasing the instantaneous risk of death by 7% and 5%, respectively. Using our model, we could anticipate the benefit of atezolizumab over chemotherapy as early as 6 months before the end of the study, which is 3 months earlier than a similar model only relying on SLD.Conclusion We showed the interest of organ-level tumor follow-up to better understand and anticipate the treatment effect on survival.

【 授权许可】

CC BY|CC BY-NC-ND