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: NCT00410124). A series of tumour response thresholds, defined by the best change in the sum of the longest tumour diameters (ΔSLD) of target lesions, was evaluated to distinguish 'responders' from 'non-responders' with respect to significant improvement in PFS. RESULTS: The optimal threshold for determining a response to everolimus was -5% ΔSLD. 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 ≥ 5% reduction in SLD is a better predictor of PFS benefit than the classical ≥ 30% reduction used with RECIST.
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: NCT00410124). A series of tumour response thresholds, defined by the best change in the sum of the longest tumour diameters (ΔSLD) of target lesions, was evaluated to distinguish 'responders' from 'non-responders' with respect to significant improvement in PFS. RESULTS: The optimal threshold for determining a response to everolimus was -5% ΔSLD. 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 ≥ 5% reduction in SLD is a better predictor of PFS benefit than the classical ≥ 30% reduction used with RECIST.
Authors: M Lamuraglia; S Raslan; R Elaidi; S Oudard; B Escudier; K Slimane; R Renard Penna; M Wagner; O Lucidarme Journal: Eur Radiol Date: 2015-05-08 Impact factor: 5.315
Authors: M H Voss; D A Bastos; C A Karlo; A Ajeti; A A Hakimi; D R Feldman; J J Hsieh; A M Molina; S Patil; R J Motzer Journal: Ann Oncol Date: 2014-01-23 Impact factor: 32.976
Authors: Abolfazl Zargari; Yue Du; Morteza Heidari; Theresa C Thai; Camille C Gunderson; Kathleen Moore; Robert S Mannel; Hong Liu; Bin Zheng; Yuchen Qiu Journal: Phys Med Biol Date: 2018-08-06 Impact factor: 3.609
Authors: Katherine M Krajewski; Marta Braschi-Amirfarzan; Pamela J DiPiro; Jyothi P Jagannathan; Atul B Shinagare Journal: Korean J Radiol Date: 2017-01-05 Impact factor: 3.500