Entry Detail
| General information | |
| Database: | DB00478 |
| Objective: | They therefore compared dovitinib with sorafenib as thirdline targeted therapies in patients with metastatic renal cell carcinoma. |
| Authors: | Motzer RJ, et al |
| Title: | Dovitinib versus sorafenib for thirdline targeted treatment of patients with metastatic renal cell carcinoma: an openlabel, randomisedphase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 24556040 |
| Trial Design | |
| Clinical Trial Id: | NCT01223027 |
| Agent: | dovitinib |
| Target: | Fibroblast growth factor receptor 3 Plateletderived growth factor receptor |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | renal cell carcinoma with a clear cell component |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | multicentre (appendix), openlabel, randomisedphase III trial, |
| Key Patients Feature: | eligible patients had metastatic renal cellcarcinoma with clear cell or a component of clear cellhistology and had received one previous VEGFtargetedtherapy (eg, sunitinib or bevacizumab) plus one previousmTOR inhibitor (eg, everolimus or temsirolimus) ineither sequence. Patients (aged more than and equal to 18 years) must have haddisease progression on or within 6 months of last therapy(VEGFtargeted agent or mTOR inhibitor therapy).Previous treatment with anticancer therapies, includingcytokines and anticancer vaccines, was permitted andwashout periods varied from 2 weeks to 6 weeksdepending on the agent (and patients had to recover fromany sideeffects from the agent). Additional inclusioncriteria included measurable disease (ResponseEvaluation Criteria in Solid Tumors [RECIST], version 1.1), Karnofsky performance status of 70 or greater, andadequate haematological, renal, and hepatic functions |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | sorafenib |
| Treatment Info: | pts were randomly assigned through an interactive voice and theyb response system to receive openlabel dovitinib (500 mg orally according to a 5dayson and 2daysoff schedule) or sorafenib (400 mg orally twice daily) in a 1:1 ratio. |
| Primary End Point: | PFS assessed by masked central review. |
| Secondary End Point: | Efficacy was assessed in all patients who were randomly assigned and safety was assessed in patients who received at least one dose of study drug. |
| Patients Number: | 284 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | The best overall response by central review was partial response (11 [4%] patients) in each of the dovitinib and sorafenib groups.More than half the patients in each group achieved stable disease (table 2). The best percentage change from baseline in sum of diameters as per central review by waterfall plot showed tumour reductions in 117 (51%) of 230 evaluable patients in the dovitinib group and 111 (46%) of 241 evaluable patients in the sorafenib group |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.7 months (95% CI 3.5-3.9) in the dovitinib group and 3.6 months (3.5-3.7) in the sorafenib group (hazard ratio 0.86, 95% CI 0.72-1.04; onesided p=0.063). |
| Median OS A vs. C: | 11.1 months (95% CI 9.5-13.4) in the dovitinib group and 11.0 months (8.6-13.5) in the sorafenib group (HR 0.96, 95% CI 0.75-1.22). Median overall survival for patients with favourable, intermediate, and poor risk MSKCC status was not reached (95% CI 12.9-not reached), 10.5 months (8.8-13.2), and 5.1 months (4.4-9.9) in the dovitinib group, respectively, and 19.3 months (12.2-19.3), 11.2 months (7.9-14.2), and 6.3 months (5.3-8.5) in the sorafenib group, respectively. |
| Adverse Event(agent arm): | Common grade 3 or 4 adverse events included hypertriglyceridaemia (38 [14%]), fatigue (28 [10%]), hypertension (22 [8%]), and diarrhoea (20 [7%]) in the dovitinib group, and hypertension (47 [17%]), fatigue (24 [8%]), dyspnoea (21 [7%]), and palmarplantar erythrodysaesthesia (18 [6%]) in the sorafenib group. The most common serious adverse event was dyspnoea (16 [6%] and 15 [5%] in the dovitinib and sorafenib groups, respectively). |
| Conclusions: | Dovitinib showed activity, but this was no better than that of sorafenib in patients with renal cell carcinoma who had progressed on previous VEGFtargeted therapies and mTOR inhibitors. This trial provides reference outcome data for future studies of targeted inhibitors in the thirdline setting. |