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)
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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). / 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.
In: EUR J CANCER, Vol. 107, 01.2019, p. 37-45.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - 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)
AU - Retz, Margitta
AU - Bedke, Jens
AU - Bögemann, Martin
AU - Grimm, Marc-Oliver
AU - Zimmermann, Uwe
AU - Müller, Lothar
AU - Leiber, Christian
AU - Teber, Dogu
AU - Wirth, Manfred
AU - Bolenz, Christian
AU - van Alphen, Robbert
AU - De Santis, Maria
AU - Beeker, Aart
AU - Lehmann, Jan
AU - Indorf, Martin
AU - Frank, Melanie
AU - Bokemeyer, Carsten
AU - Gschwend, Jürgen E
N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.ejca.2018.11.001
DO - 10.1016/j.ejca.2018.11.001
M3 - SCORING: Journal article
C2 - 30529901
VL - 107
SP - 37
EP - 45
JO - EUR J CANCER
JF - EUR J CANCER
SN - 0959-8049
ER -
