BACKGROUND: Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria.
The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown.
PATIENTS AND METHODS: mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) < 70%, nonclear-cell histology, brain metastases, hemoglobin ≤ 9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of < 100 × 103/uL, or neutrophil count < 1500/mm3.
RESULTS: Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039). When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95% confidence interval 1.378-1.751, P < 0.0001).
CONCLUSIONS: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.
Written by:
Heng DY, Choueiri TK, Rini BI, Lee J, Yuasa T, Pal SK, Srinivas S, Bjarnason GA, Knox JJ, Mackenzie M, Vaishampayan UN, Tan MH, Rha SY, Donskov F, Agarwal N, Kollmannsberger C, North S, Wood LA. Are you the author?
Tom Baker Cancer Center, Calgary, AB, Canada.
Reference: Ann Oncol. 2014 Jan;25(1):149-54.
doi: 10.1093/annonc/mdt492
PubMed Abstract
PMID: 24356626
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