Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial

Summary Background In previous clinical trials of patients with metastatic renal-cell carcinoma, patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib. We therefore undertook a phase 3 trial comparing axitinib with sorafen...

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Bibliographic Details
Published in:The lancet oncology 2013-12, Vol.14 (13), p.1287-1294
Main Authors: Hutson, Thomas E, Prof, Lesovoy, Vladimir, Prof, Al-Shukri, Salman, Prof, Stus, Viktor P, Prof, Lipatov, Oleg N, Prof, Bair, Angel H, PhD, Rosbrook, Brad, MS, Chen, Connie, PharmD, Kim, Sinil, MD, Vogelzang, Nicholas J, Prof
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic Agents - adverse effects
Antineoplastic Agents - therapeutic use
Blood pressure
Cancer
Carcinoma, Renal Cell - drug therapy
Carcinoma, Renal Cell - pathology
Clinical outcomes
Confounding Factors (Epidemiology)
Cytokines
Disease-Free Survival
Drug dosages
Europe
Female
Hematology, Oncology and Palliative Medicine
Humans
Hypotheses
Imidazoles - adverse effects
Imidazoles - therapeutic use
Indazoles - adverse effects
Indazoles - therapeutic use
Kidney Neoplasms - drug therapy
Kidney Neoplasms - pathology
Male
Metastasis
Middle Aged
Niacinamide - adverse effects
Niacinamide - analogs & derivatives
Niacinamide - therapeutic use
North America
Odds Ratio
Patients
Phenylurea Compounds - adverse effects
Phenylurea Compounds - therapeutic use
Protein Kinase Inhibitors - therapeutic use
Research Design
Scintigraphy
Severity of Illness Index
Thyroid gland
Treatment Outcome
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Summary:Summary Background In previous clinical trials of patients with metastatic renal-cell carcinoma, patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib. We therefore undertook a phase 3 trial comparing axitinib with sorafenib in patients with treatment-naive metastatic renal-cell carcinoma. Methods In this randomised, open-label, phase 3 trial, patients with treatment-naive, measurable, clear-cell metastatic renal-cell carcinoma from 13 countries were stratified by Eastern Cooperative Oncology Group performance status, and then randomly assigned (2:1) by a centralised registration system to receive axitinib 5 mg twice daily, or sorafenib 400 mg twice daily. The primary endpoint was progression-free survival, assessed by masked independent review committee in the intention-to-treat population. This ongoing trial is registered at ClinicalTrials.gov , NCT00920816. Findings Between June 14, 2010, and April 21, 2011, we randomly assigned 192 patients to receive axitinib, and 96 patients to receive sorafenib. The cutoff date for this analysis was July 27, 2012, when 171 (59%) of 288 patients died or had disease progression, as assessed by the independent review committee. There was no significant difference in median progression-free survival between patients treated with axitinib or sorafenib (10·1 months [95% CI 7·2–12·1] vs 6·5 months [4·7–8·3], respectively; stratified hazard ratio 0·77, 95% CI 0·56–1·05). Any-grade adverse events that were more common (≥10% difference) with axitinib than with sorafenib were diarrhoea (94 [50%] of 189 patients vs 38 [40%] of 96 patients), hypertension (92 [49%] vs 28 [29%]), weight decrease (69 [37%] vs 23 [24%]), decreased appetite (54 [29%] vs 18 [19%]), dysphonia (44 [23%] vs ten [10%]), hypothyroidism (39 [21%] vs seven [7%]), and upper abdominal pain (31 [16%] vs six [6%]); those more common with sorafenib than with axitinib included palmar-plantar erythrodysaesthesia (PPE; 37 [39%] of 96 patients vs 50 [26%] of 189), rash (19 [20%] vs 18 [10%]), alopecia (18 [19%] vs eight [4%]), and erythema (18 [19%] vs five [3%]). The most common grade 3 or 4 adverse events in patients treated with axitinib included hypertension (26 [14%] of 189 patients), diarrhoea (17 [9%]), asthenia (16 [8%]), weight decrease (16 [8%]), and PPE (14 [7%]); common grade 3 or 4 adverse events in patients treated with sorafenib included PPE (15 [16%] of 96 patients), diarrho
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(13)70465-0