Clinical Trial Participants With Metastatic Renal Cell Carcinoma Differ From Patients Treated in Real-World Practice.
OBJECTIVE
Although narrow eligibility criteria improve the internal validity of clinical trials, they may result in differences between study populations and real-world patients, threatening generalizability. Therefore, we evaluated whether patients treated for metastatic renal cell cancer (mRCC) in routine clinical practice are similar to those enrolled onto clinical trials.


METHODS
In this cohort study, we compared baseline characteristics of patients with mRCC in phase III clinical trials of new targeted therapies and those in a retrospective registry composed of academic (Duke) and community (ACORN Network) practices.


RESULTS
A total of 438 registry patients received sunitinib, sorafenib, temsirolimus, or pazopanib (most commonly used agents) in first-line treatment. Registry patients receiving tyrosine kinase inhibitors (sunitinib, sorafenib, or pazopanib) were more likely to have poor-risk disease by Memorial Sloan Kettering Cancer Center criteria (poor, 7.4% v 2.9%; P < .001; favorable, 30.1% v 43.8%; P < .001) and to have impaired performance status (Eastern Cooperative Oncology Group > 1, 11.1% v 0.6%; P < .001). However, registry patients receiving temsirolimus were less likely to have poor-risk disease (poor, 10.2% v 69.4%; P < .001; favorable, 16.9% v 0%; P < .001). Thus, 39.0% of registry patients would have been excluded from the phase III clinical trial testing the drug they received.


CONCLUSIONS
Patients with mRCC treated with tyrosine kinase inhibitors in real-world clinical practice are sicker than those enrolled onto pivotal clinical trials, and more than one third are trial ineligible. Application of clinical trial findings to dissimilar populations may result in patient harm. Clinical research with more inclusive eligibility criteria is needed to appropriately guide real-world practice.
Duke University Medical Center; Duke Clinical Research Institute, Durham, NC; and ACORN Research, Memphis, TN.
Aaron P
AP
Mitchell
Duke University Medical Center; Duke Clinical Research Institute, Durham, NC; and ACORN Research, Memphis, TN.
Michael R
MR
Harrison
Duke University Medical Center; Duke Clinical Research Institute, Durham, NC; and ACORN Research, Memphis, TN.
Mark S
MS
Walker
Duke University Medical Center; Duke Clinical Research Institute, Durham, NC; and ACORN Research, Memphis, TN.
Daniel J
DJ
George
Duke University Medical Center; Duke Clinical Research Institute, Durham, NC; and ACORN Research, Memphis, TN.
Amy P
AP
Abernethy
Duke University Medical Center; Duke Clinical Research Institute, Durham, NC; and ACORN Research, Memphis, TN Brad.Hirsch@usoncology.com.
Bradford R
BR
Hirsch
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010361:Patients / Q000706:statistics & numerical data*; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012720:Severity of Illness Index; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib
D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; C401859:temsirolimus; C516667:pazopanib; D000077157:Sorafenib; D000077210:Sunitinib; D020123:Sirolimus