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- Document type:
- Journal Article
- Author(s):
- Retz, Margitta; Bedke, Jens; Bögemann, Martin; Grimm, Marc-Oliver; Zimmermann, Uwe; Müller, Lothar; Leiber, Christian; Teber, Dogu; Wirth, Manfred; Bolenz, Christian; van Alphen, Robbert; De Santis, Maria; Beeker, Aart; Lehmann, Jan; Indorf, Martin; Frank, Melanie; Bokemeyer, Carsten; Gschwend, Jürgen E
- Title:
- SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11).
- Abstract:
- This trial compared the sequential therapy with the multikinase inhibitor sorafenib (So) followed by pazopanib (Pa) or vice versa in advanced/metastatic renal cell carcinoma (mRCC) patients.This multicenter, randomized phase 3 study assessed the sequential use of So-Pa versus Pa-So in patients with mRCC without prior systemic therapy. Pts were randomized to So 2 × 400 mg/day followed by Pa 1 × 800 mg/day in case of progression or intolerable toxicity or vice versa. Primary endpoint was total PFS (tPFS), defined as time from randomization to progression, or death during second-line therapy. Key secondary endpoints included overall survival (OS), first-line PFS, disease control rate (DCR) and safety.A total of 377 pts were randomized (So-Pa, n = 189; Pa-So, n = 188). Recruitment of a total 544 pts was calculated, but actual accrual rate turned out to be lower than expected. The primary endpoint median tPFS was 8.6 mo (95% CI 7.7-10.2) for So-Pa and 12.9 mo (95% CI 10.8-15.2) for Pa-So with a hazard ratio (HR) of 1.36 (upper limit of one-sided 95% CI 1.68), which exceeded a predefined HR <1.225 as a one-sided 95% confidence interval. Non-inferiority of So-Pa regarding tPFS was not met. Secondary endpoints displayed marked statistical differences in favor of Pa-So in first-line PFS and DCR but not for OS and 2nd-line PFS. Side effect profiles were consistent with known toxicities of the respective multikinase-inhibitor including diarrhea, fatigue, hand-foot skin reaction and hypertension.Non-inferiority of the primary endpoint tPFS could not be demonstrated for So-Pa. The results for first-line PFS and DCR favored the Pa-So sequence.NCT01613846, www.clinicaltrials.gov.
- Journal title abbreviation:
- Eur J Cancer
- Year:
- 2019
- Journal volume:
- 107
- Pages contribution:
- 37-45
- Fulltext / DOI:
- doi:10.1016/j.ejca.2018.11.001
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/30529901
- Print-ISSN:
- 0959-8049
- TUM Institution:
- Urologische Klinik und Poliklinik
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