Tuesday, April 15, 2014

What is the best sequencing for sorafenib and sunitinib?

The Phase 3 Randomized Sequential Open-Label Study to
Evaluate the Efficacy and Safety of Sorafenib Followed by
Sunitinib Versus Sunitinib Followed by Sorafenib in the
Treatment of First-Line Advanced/Metastatic Renal Cell
Carcinoma (SWITCH) trial was the first study to prospectively
evaluate whether there or not there is an advantage to the
sequence of sorafenib followed by sunitinib (SO/SU) compared
to sunitinib followed by sorafenib (SU/SO). The primary results
of this study were presented at GU-ASCO 2014.1
The study, initiated in 2008, enrolled a total of 365 patients
with metastatic RCC (mRCC) who had not previously received
systemic therapy and were deemed to be unsuitable for cytokine
therapy. Patients were randomized 1:1 to receive sunitinib or
sorafenib. Patients were switched to the other therapy if they
experienced disease progression or intolerable toxicity. The
primary end point was the total progression-free survival (T-PFS)
from the time of initial randomization to confirmed progression
or death during second-line therapy. There were a number
of secondary end points presented as well, including overall
survival (OS), PFS in first-line treatment, PFS in second-line
treatment and objective response rate. Safety and tolerability
were also assessed.
At baseline, the 2 arms were well-balanced in terms of
demographics and disease characteristics, with no statistically
significant differences between treatment arms. At time of final

T-PFS analysis, there was no statistically significant difference
in T-PFS between treatment arms. The median T-PFS was 14.9
months for SU/SO and 12.5 months for SO/SU (hazard ratio
[HR] 1.01, p = 0.54). There was also no significant difference
between arms for OS (median 31.5 months for SO/SU and
30.2 months for SU/SO; HR 1.00, p = 0.49) (Fig. 1). However,

more patients in the SO/SU arm reached second-line therapy
compared to those in the SU/SO arm (57% vs. 42%, p < 0.01)
and the second-line PFS was significantly longer for the SO/
SU arm (median 5.4 months) compared to the SU/SO arm (2.8
months). The authors stressed that these results must be interpreted
with caution, however, due to the imbalance between
arms for patients initiating protocol-defined second-line therapy
and the fact that there was no randomization immediately
prior to the second line. There were also some differences in
tolerability profiles, with diarrhea and hand-foot skin reaction
being considerably higher in the SO/SU arm, while nausea and
stomatitis were more common in the SU/SO arm.
This study concludes that both sequences achieved comparable
PFS and OS with similar toxicity safety profiles, and further
illustrates the ongoing need to determine the best sequencing
strategies to optimize outcomes for mRCC patients.



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