696 844
expressed on RCC tumor cells
[8]. Durable complete
remission is rarely observed for TKIs, and discontinuation
of TKIs frequently results in disease relapse in a substantial
number of RCC patients
[9]. In
[14_TD$DIFF]
the light of this knowledge,
the recent positive S-TRAC study raises questions about
long-term clinical significance. The goal of adjuvant
therapies is to eradicate micro-metastases and thereby
prevent disease relapse. However, owing to their known
biological activity and experience from clinical praxis, it
seems plausible that discontinuation of TKIs after 1 yr may
lead to metastatic regrowth if the cytostatic mode of action
is the key driver in TKI therapy. Therefore, it can be
speculated that the DFS advantage of 12 mo observed is
merely related to the time of the treatment period within
the S-TRAC trial.
Following this hypothesis, all patients with high-risk
disease would have to be treated until disease relapse to
maximize DFS. This is not justifiable
[15_TD$DIFF]
with
[16_TD$DIFF]
regard of the
known rate of side effects, treatment costs, and the
substantial number of patients (at least 50%) who will
never experience disease relapse. In addition, use of TKIs in
the adjuvant setting raises concerns regarding the develop-
ment of TKI resistance.
These hypotheses remain speculative until final OS data
are presented for the S-TRAC trial. However, it would
be desirable to find an adjuvant agent that can induce
long-term metastatic control. Immunologic treatment
approaches are promising and represent great hope in this
context, although previous adjuvant trials with immuno-
logic agents have not been successful. The most recent
negative trial that investigated an immunologic approach
for adjuvant treatment of RCC was ARISER. This study
investigated the monoclonal antibody girentuximab, which
is directed against carbonic anhydrase IX (a cell-surface
protein frequently overexpressed in ccRCC but not in
healthy kidney tissue) in intermediate- and high-risk ccRCC
[10] .The
[3_TD$DIFF]
primary endpoint
[17_TD$DIFF]
DFS was not prolonged.
However, a significant DFS benefit was observed in several
subgroups
[10] .New immunologic treatment approaches
with proven efficacy in advanced and metastatic disease
have been introduced into clinical practice during the past
year. These therapeutic agents demonstrated durable long-
term tumor responses for several cancer entities. Different
agents targeting the programmed death receptor and its
ligand are likely to be investigated in the adjuvant setting in
the near future. It is expected that these compounds could
provide a solid adjuvant treatment option and that possible
treatment with TKIs in the adjuvant setting is just an
interim solution towards emerging from the desert for
adjuvant treatment of RCC.
Conflicts of interest:
Jens Bedke has received consultancy fees,
honoraria, or study participation fees from Bayer, BMS, GSK, Immatics,
Novartis, Pfizer, and Roche. Arnulf Stenzl has received consultancy fees,
honoraria, or study participation fees from Bayer, BMS, Immatics,
Novartis, Pfizer, and Roche. Nils Kro¨ger has received consultancy fees,
honoraria, or study participation fees from BMS, Novartis, and Pfizer.
Martin Burchardt has nothing to disclose.
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