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). (January 2019)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: European journal of cancer. Volume 107(2019)
• Page Start: 37
• Page End: 45
• Publication Date: 2019-01
• Subjects: Renal cell carcinoma (RCC) -- Sequential therapy -- Sorafenib -- Pazopanib -- Tyrosine-kinase inhibitor; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.11.001
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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 . Highlights: SWITCH II is a phase III study of sequential therapy with Sorafenib (So). Pazopanib (Pa) vs Pa-So for advanced RCC. The primary endpoint of non-inferiority of total PFS (tPFS) for So-Pa was not met. Sequential therapy with Pa-So resulted in longer median tPFS (12.9 vs 8.6 months) and median OS (28.0 vs 22.7 months).