The Lynx Group

Many Patients with mRCC Ineligible for Clinical Trials

March 2012, Vol 3, No 2

San Francisco, CA—A large number of patients with metastatic renal-cell carcinoma (mRCC) are ineligible for clinical trials and their clinical outcomes are inferior to those of patients who are trial eligible, according to a study presented at the 2012 Genitouri nary Cancers Symposium. The data were presented by the International mRCC Database Con sorti um, a group that analyzed data from 17 international cancer centers on consecutive series of patients with mRCC. Clinical trials have strict eligibility criteria to maintain internal validity. “Many patients in everyday practice may not meet these criteria, yet in clinical practice, the results of these trials are being extrapolated to all patients with mRCC being treated with targeted therapy,” said Daniel Heng, MD, MPH, Medical Oncologist, Tom Baker Cancer Center, University of Calgary, Alberta, and lead investigator of the study. The consortium estimated the number of trial-ineligible patients who received targeted therapy and compared their outcomes with those of trial-eligible patients from the 17 cancer centers.

Patients received antivascular endothelial growth factor–targeted therapy for mRCC, which included sunitinib, sorafenib, bevacizumab, pazopanib, and axitinib. Patients were retrospectively deemed ineligible for clinical trials based on frequently used inclusion/ exclusion criteria. All other patients were assumed to be potentially eligible for clinical trials. The frequently used exclusion criteria were a Karnofsky Performance Status (KPS) score <70%, brain metastases, non–clear-cell histology, hemoglobin ≤9 g/dL, creatinine >2 times the upper limit of normal, platelet count <100 × 103/μL, a neutrophil count <1500/mm3, and corrected calcium ≤12 mg/dL. Of 2076 patients with mRCC who received targeted therapy, 894 (43%) were deemed ineligible. The most frequent (13%) reason for exclusion was a KPS score <70%. More than twice as many patients deemed ineligible for clinical trials as those who were potentially eligible had a poor prognosis (43% vs 16%, respectively), said Dr Heng; 25% of eligible patients had favorable-risk disease compared with only 9% of ineligible patients.

The response rate to therapy was significantly worse in ineligible versus eligible patients (21% vs 29%, respectively). Response rates were worse in ineligible patients for all prognostic categories defined by Dr Heng and colleagues. The median progression-free survival (PFS) with first-line targeted therapy was 5.2 months for ineligible patients versus 8.8 months for eligible patients, and the median overall survival (OS) was 14.5 months versus 28.8 months, respectively (all P <.001). Of the 896 patients who continued to second-line therapy, PFS was 3.2 months in the trial-ineligible patients versus 4.4 months in the trial-eligible patients. When adjusted by prognostic categories, the hazard ratio for death between the trial-ineligible and trialeligible patients was 1.511. “The discrepancies in clinical outcome should be taken into account when applying protocol therapies to protocol-ineligible patients,” said Dr Heng. “These patients should still be treated with targeted therapy, but when it comes to patient counseling and prognostication, we should temper those discussions with these data.” Specific trials addressing the needs of protocol-ineligible patients and assessing OS are required, he said.

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