According to results of the SWITCH, a randomised sequential open-label study, that evaluated efficacy and safety of sorafenib/sunitinib vs. sunitinib/sorafenib in the treatment of metastatic renal cell cancer (mRCC), there is no difference whether patients first start on sorafenib and then switch to sunitinib upon progression or vice versa. Progression-free survival (PFS) and overall survival (OS) outcomes across the two sequences were similar, as reported by lead investigator Dr Maurice-Stephan Michel of the University Medical Center Mannheim and the University of Heidelberg in Germany. The findings were reported at 2014 Genitourinary Cancer Symposium in San Francisco, USA (30 January-1 February).
The sequential use of sorafenib and sunitinib has been investigated retrospectively in patients with mRCC. But the SWITCH is first randomised study that prospectively compared sorafenib/sunitinib vs. sunitinib/sorafenib in the first-line setting. The study was initiated in 2008; it is a phase III trial specifically designed as a superiority study intended to demonstrate the supremacy of sorafenib-sunitinib over sunitinib-sorafenib.
Patients with mRCC, unsuitable for cytokines, without prior systemic therapy, ECOG performance score 0/1, MSKCC score low or intermediate, and ≥1 measurable lesion were randomised to receive open-label sorafenib/sunitinib (arm A) or sunitinib/sorafenib (arm B) in standard dosage. A primary endpoint was total PFS from randomisation to event during second-line therapy. Therapy was continued until progression or intolerability.
The study was conducted in Germany, Austria, and the Netherlands with 365 patients enrolled: 182 in arm A and 183 in arm B. The two arms were well balanced in term of median age, prior nephrectomy, MSKCC score, and clear cell histology.
At time of final total PFS analysis, 220 events had occurred with no statistically significant difference in total PFS across arms. Therefore, the study did not meet the primary endpoint demonstrating superiority of sorafenib-sunitinib over sunitinib-sorafenib for total PFS measured over the two sequential therapies. The median total PFS duration reached 12.5 months in the sorafenib-sunitinib arm and 14.9 months in the sunitinib-sorafenib arm.
Although there was no statistically significant difference in median OS (31.5 months in the sorafenib-sunitinib arm and 30.2 months in the sunitinib-sorafenib arm), the OS duration beyond 30 months in both arms is among the longest yet reported, according to study authors.
Median PFS on first-line therapy proved similar between two arms (5.9 vs. 8.5 months). Although second-line PFS did show a difference (5.4 vs. 2.8 months; HR 0.55; p < 0.001), this finding should be interpreted with caution due to an imbalance and lack of random assignment for patients receiving protocol-defined second-line treatment.
The overall disease control rate with first-line treatment was similar with sorafenib and sunitinib. Fewer patients crossed over to receive sorafenib in arm B than to receive sunitinib in arm A.
As expected, the side effect profiles of the treatment regimens differed, but side effects were generally less frequent during second-line therapy. Most frequent (>20%) side effects under front-line treatment sorafenib vs. sunitinib were alopecia, diarrhoea, dysgeusia, fatigue, hand-foot-syndrome reaction, hypertension, nausea and rash.
The authors concluded that both drugs provided overall benefit regardless of therapy sequence. Side effect profiles were different and less frequent during second-line therapy. More patients reached second-line in the sorafenib/sunitinib arm.
Disclosures of the abstract authors:
Maurice Stephan Michel: Honoraria - Astellas Pharma; Bayer; Novartis
Walter Vervenne: No relevant relationships to disclose
Maria de Santis: Consultant or Advisory Role - Astellas Pharma; Bayer; GlaxoSmithKline; Novartis; Pfizer; Pierre Fabre Medicament; Roche; Honoraria - Bayer; Exelixis; GlaxoSmithKline; Novartis; Pfizer; Roche; Sanofi; Research Funding - Pierre Fabre Medicament
Ludwig Fischer von Weikersthal: No relevant relationships to disclose
Peter J. Goebell: Honoraria - Amgen; Bayer; Bristol-Myers Squibb; GlaxoSmithKline; Novartis; Pfizer; Roche
Juergen Lerchenmueller: No relevant relationships to disclose
Uwe Zimmermann: Other Remuneration - DGU German Association of Urology
Monique M.E.M. Bos: No relevant relationships to disclose
Werner Freier: No relevant relationships to disclose
Silke Schirrmacher-Memmel: No relevant relationships to disclose
Michael D. Staehler: Consultant or Advisory Role – Bayer; Honoraria – Bayer; Research Funding - Bayer
Sascha Pahernik: No relevant relationships to disclose
Maartje Los: No relevant relationships to disclose
Marcus Schenck: No relevant relationships to disclose
Anne Flörcken: Honoraria - Bayer; GlaxoSmithKline; Pfizer
Cornelis Van Arkel: No relevant relationships to disclose
Kirsten Hauswald: No relevant relationships to disclose
Martin Indorf: No relevant relationships to disclose
Dana Gottstein: No relevant relationships to disclose
Christian Eichelberg: Consultant or Advisory Role - Bayer (U); GlaxoSmithKline; Novartis; Pfizer; Honoraria - Bayer; GlaxoSmithKline; Novartis; Pfizer; Research Funding - Bayer; GlaxoSmithKline; immatics; Novartis; Pfizer; Wilex; Other Remuneration - Bayer; Novartis; Pfizer
Michel SM, Vervenne W, de Santis M et al. SWITCH: A randomized sequential open-label study to evaluate efficacy and safety of sorafenib (SO)/sunitinib (SU) versus SU/SO in the treatment of metastatic renal cell cancer (mRCC). J Clin Oncol 32, 2014 (suppl 4; abstr 393).