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

• Published in: European journal of cancer (1990) 2012-07, Vol.48 (10), p.1512-1518
• Main Authors: Oudard, Stéphane, Thiam, Rokhaya, Fournier, Laure S, Medioni, Jacques, Lamuraglia, Michele, Scotte, Florian, Fabre, Elizabeth, Kim, Dennis, Kpamegan, Euloge, Panneerselvam, Ashok, Cuenod, Charles A
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinoma, Renal Cell - drug therapy; Disease-Free Survival; Everolimus; Hematology, Oncology and Palliative Medicine; Humans; Immunosuppressive Agents - therapeutic use; Kidney cancer; Kidney Neoplasms - drug therapy; Medical sciences; mTOR; Oncology; Pharmacology. Drug treatments; Proportional Hazards Models; RAD001; RECIST; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Sequential therapy; Sirolimus - analogs & derivatives; Sirolimus - therapeutic use; Targeted therapy; Time Factors; Treatment Outcome; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2012.01.027

Abstract 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.