Association between treatment effects on disease progression end points and overall survival in clinical studies of patients with metastatic renal cell carcinoma

• Published in: British journal of cancer Vol. 107; no. 7; pp. 1059 - 1068
• Main Authors: Delea, T E, Khuu, A, Heng, D YC, Haas, T, Soulières, D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.09.2012; Nature Publishing Group
• Subjects: 631/67/322; 692/699/67/1059; 692/699/67/589/1588/1351; 692/700/1750/1976; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cancer therapies; Carcinoma, Renal Cell - drug therapy; Clinical Study; Clinical trials; Cytokines; Disease Progression; Disease-Free Survival; Drug Resistance; Endpoint Determination; Epidemiology; Humans; Kidney cancer; Kidney Neoplasms - drug therapy; Kidneys; Medical research; Medical sciences; Metastasis; Molecular Medicine; Molecular Targeted Therapy; Nephrology. Urinary tract diseases; Oncology; Randomized Controlled Trials as Topic; Regression analysis; Risk reduction; Survival; Survival Analysis; Treatment Outcome; Tumors; Tumors of the urinary system; Canada; progression; renal cell carcinoma; metastatic; survival; Kidney disease; Human; Urinary system disease; Carcinoma; Malignant tumor; Metastasis; Survival; Cancerology; Treatment; Kidney cancer; Grawitz tumor; Advanced stage; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.367

Background: The relationship between progression-free survival and time to progression (PFS/TTP) and overall survival (OS) has been demonstrated in a variety of solid tumours but not in metastatic renal cell carcinoma (mRCC). Methods: A systematic literature search was conducted to identify controlled trials of cytokine or targeted therapies for mRCC reporting information on treatment effects on PFS/TTP and OS for one or more comparison. The associations between treatment effects on PFS/TTP and OS were analysed using linear regression. Results: Thirty-one studies representing 10 943 patients, 75 treatment groups, and 41 comparisons were identified. The correlation coefficient between the negative log of the hazard ratio (HR) for PFS/TTP (−ln HR PFS/TTP ) vs the negative log of the HR for OS (−ln HR OS ) was 0.80 ( P <0.0001). In linear regression, the coefficient on −ln HR PFS/TTP vs −ln HR OS was 0.64 (95% confidence interval (CI): 0.47 0.81; R 2 =0.63), suggesting each 10% relative risk reduction (RRR) for PFS/TTP was associated with a 6% RRR for OS. A 1-month gain in median PFS/TTP was associated with a 1.17-month gain in median OS (95% CI: 0.59,1.76; R 2 =0.28). Conclusion: In trials of treatments for mRCC, treatment effects on PFS/TTP are strongly associated with treatment effects on OS.