Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: Analysis of response and progression-free survival in the RECORD-1 study

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• 作者：Sté ; phane Oudard^a ; ^{stephane.oudard@egp.aphp.fr} ; Rokhaya Thiam^b ; Laure S. Fournier^b ; Jacques Medioni^a ; Michele Lamuraglia^a ; Florian Scotte^b ; Elizabeth Fabre^a ; Dennis Kim^c ; Euloge Kpamegan^d ; Ashok Panneerselvam^d ; Charles A. Cuenod^b
• 关键词：Kidney cancer ; mTOR ; Oncology ; RAD001 ; RECIST ; Targeted therapy ; Sequential therapy
• 刊名：European Journal of Cancer
• 出版年：2012
• 期刊代码：88_09598049
• 类别：med
• 出版时间：July, 2012
• 卷：48
• 期：10
• 页码：1512-1518
• 文件大小：421 K

摘要

Background and objectives

Objective response as determined by Response Evaluation Criteria in Solid Tumors (RECIST) is low among patients with metastatic renal cell carcinoma (mRCC) treated with targeted agents, despite significantly improved progression-free survival (PFS). A modified response threshold may be more clinically meaningful than RECIST for identifying patients who may derive a PFS benefit from targeted therapy.

Patients and methods

We performed a retrospective analysis of data from the phase III RECORD-1 trial of everolimus versus placebo in patients with mRCC who had failed sunitinib or sorafenib (ClinicalTrials.gov identifier: ). A series of tumour response thresholds, defined by the best change in the sum of the longest tumour diameters (螖SLD) of target lesions, was evaluated to distinguish 鈥榬esponders鈥?from 鈥榥on-responders鈥?with respect to significant improvement in PFS.

Results

The optimal threshold for determining a response to everolimus was 鈭?%螖SLD. At this threshold, median PFS was 8.4 months in responders and 5.0 months in non-responders (hazard ratio [HR] 2.4, 95%confidence interval [CI] 1.6-3.7).

Conclusion

In patients who have failed vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy, everolimus affords superior PFS to placebo, regardless of change in tumour burden. However, a 猢?%reduction in SLD is a better predictor of PFS benefit than the classical 猢?0%reduction used with RECIST.