A new report published by Knudsen et al in PLOS ONE focused on the clinical validation of a drug response predictor (DRP) biomarker algorithm for dovitinib, a receptor tyrosine kinase inhibitor of VEGFR1–3, PDGFR, FGFR1/3, c-KIT, FLT3, and topoisomerase 1 and 2. Data showed that the DRP-dovitinib tool was able to identify a subgroup of patients with advanced renal cell carcinoma (RCC) with improved clinical benefit from dovitinib treatment compared with unselected patients.
“This is the first validated predictive biomarker in renal cell carcinoma, a long-standing goal in potentially improving the treatment of these patients. An additional prospective trial would be required before patients [with RCC who] are candidates for dovitinib can benefit from this diagnostic breakthrough…,” commented first study author Steen Knudsen, PhD.
The DRP-dovitinib tool is a complex transcriptomic signature comprising 58 mRNA biomarkers that are collectively predictive of tumor response to the drug. In the study—which evaluated pretreatment biopsies from 135 patients with advanced RCC—the DRP-positive subgroup (n = 49) had a median overall survival of 15 months (95% confidence interval [CI] = 12.94–26.25 months), whereas the DRP-negative subgroup (n = 86) had a median overall survival of 9.13 months (95% CI = 7.49–13.2 months). The hazard ratio was 0.60 (95% CI = 0.39–0.91).
The DRP-dovitinib tool showed similar data in various other solid tumors, such as hepatocellular carcinoma, thereby demonstrating that its functionality may be independent of tumor type and has applicability beyond RCC.
The study authors concluded: “The DRP-dovitinib [tool] shows promise as a potential biomarker for identifying [patients with] advanced RCC most likely to experience clinical benefit from dovitinib treatment, subject to confirmation in an independent prospective trial of dovitinib in patients with RCC.”
Disclosure: For full disclosures of the study authors, visit journals.plos.org.
