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)
Purpose - 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. - Methods - This multicenter, randomized phase 3 study assessed the sequential use of So-Pa versus...
Gespeichert in:
| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2019
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| In: |
European journal of cancer
Year: 2019, Jahrgang: 107, Pages: 37-45 |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2018.11.001 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1016/j.ejca.2018.11.001 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0959804918314540 
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| Verfasserangaben: | Margitta Retz, Jens Bedke, Martin Bögemann, Marc-Oliver Grimm, Uwe Zimmermann, Lothar Müller, Christian Leiber, Dogu Teber, Manfred Wirth, Christian Bolenz, Robbert van Alphen, Maria De Santis, Aart Beeker, Jan Lehmann, Martin Indorf, Melanie Frank, Carsten Bokemeyer, Jürgen E. Gschwend |
| Zusammenfassung: | Purpose - 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. - Methods - 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. - Results - 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. - Conclusions - 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. - Trial registration - NCT01613846, www.clinicaltrials.gov. |
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| Beschreibung: | Available online 7 December 2018 Gesehen am 01.08.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2018.11.001 |