20 / 32
Novel treatment options for RCC: a review
Interview with Bradley G Somer
MD
Dr Jennifer Caudle speaks with Dr Somer, Assistant Professor in the Department of Hematology/Oncology
at the University of Tennessee Health Science Center and Senior Partner at West Clinic in Memphis, on
pembrolizumab plus IDO1 inhibition for advanced renal cell carcinoma, and the ProtecT trial involving
VEGF-directed therapy.
Dr Caudle:
You and your colleagues pre-
sented data related to the combination
of pembrolizumab and an IDO inhibitor
in patients with advanced kidney cancer.
Can you tell us about this dataset and its
implication for this disease? In particular, is
combination immunotherapy a viable strat-
egy in renal cell carcinoma, and how might
this combination compare to nivolumab/
ipilimumab?
Dr Somer:
A lot of questions there. I’m going
to tackle them one by one.
This dataset was an expansion cohort of
the combination of pembrolizumab and
a drug called epacadostat, an oral agent
that is an IDO1 inhibitor. Now the big rage
is trying to find combination immunother-
apies… and this was an expansion cohort
of renal cell carcinoma; clear cell carci-
noma patients [and] most had received
prior therapy.
An IDO essentially is an immune regula-
tory molecule, an enzyme that actually
metabolizes tryptophan in the tumor
microenvironment. When that happens,
it essentially creates an immune suppres-
sive effect on the local area. For example,
the placenta makes a lot of IDO so that a
mother’s immune system can’t detect the
placenta. Tumor utilizes that mechanism to
make itself invisible to the immune system.
By using this drug (epacadostat) to block
IDO, it can regulate the immune system to
enable it to work more effectively. When it
gets combined with pembrolizumab, which
also is an immune checkpoint inhibitor,
that’s a combined immune effect. Basically
the point of this study was to look for what
might be considered an enhanced activ-
ity, and then looking at the potential safety
effects of it. Their efficacy was looked at
in 30 patients with clear cell carcinoma of
the kidney. A third of the patients had a
response and about 50% or so had a clin-
ical benefit.
What was interesting was that if you looked
at the patients who had zero to one prior
line of therapy, it was about 47% response
and close to 60% clinical benefit. If you look
at just the checkpoint inhibitor alone, like
nivolumab for example, probably about
15% to 25% response. So looking at some-
thing that might provide 33% response or
50% response, that’s kind of pushing it
beyond where you might get with just a sin-
gle-agent checkpoint inhibitor. So it lends
at least the possibility that this combination
effect is real, and hopefully to go into the
next phase of development.
The added bonus is that epacadostat
doesn’t really add that much to toxicity to
what you might see with a checkpoint inhib-
itor alone. Maybe a little more rash, but it
seems that the side effect profile was very
similar to what you might expect with pem-
brolizumab alone, so it looks promising.
What I was going to say also, you men-
tioned other combination immunotherapy
like nivolumab with ipilimumab, there’s
some early data showing good response
with that too; enhanced response at like
40% or so. There’s added toxicity when you
combine it with ipilimumab. The main thing
[we’re] looking at now is what combina-
tion therapy works the best with the least
amount of side effects. I think the jury’s still
out on that, but there’s clear proof of con-
cept to push this to the next level.
Dr Caudle:
Data from the ProtecT clinical
trial is being presented at this meeting.
Can you tell us a little bit more about how
this dataset will affect your clinical practice
for patients with localized kidney cancer?
Are there any patients for whom you might
consider adjuvant VEGF-directed therapy?
DrSomer:
This is a very interesting story in the
sense that we know adjuvant therapy, in a
lot of solid tumors there’s clear benefit. But
Practice changers inmyeloma
Interview with Rafael D. Fonseca MD
Dr Farzanna Haffizulla speaks with Dr Fonseca, Chair of the Department of
Internal Medicine at the Mayo Clinic, on novel combinations for the treatment
of myeloma and whether these could form the new standard of care for
front-line therapy.
Dr Haffizulla:
A number of studies this year
report the use of novel combinations up
front for the treatment of myeloma. How
close are we to a new standard of care for
front-line therapy?
Dr Fonseca:
That’s a great way to phrase
that question. It goes without saying that
we’re getting better and better at achiev-
ing very deep responses, very durable
responses as well too in the front-line
setting. And the questions right now are
what are the best agents, how should they
be combined, and of course, the second
part of the question is should we be add-
ing monoclonal antibodies? Actually, this
morning we saw two presentations, one
where they added elotuzumab, one where
daratumumab was added, and it’s a little
bit early to say whether any of those actu-
ally changed the standard of care at this
point. But we’ve learned that the combina-
tions of carfilzomib with lenalidomide and
dexamethasone are very, very active and
I think that’s probably the most pressing
question, at what point should that become
the standard front-line therapy and the sec-
ond question of course is the daratumumab
question. Everyone is very interested.
Dr Jakubowiak presented a study in that
regard and an impressive result, but the
reason I say it’s harder because there are
so many options and we just want to get
really smart about how we go about com-
bining these agents. During the session,
I was thinking about this and they were
presenting so many clinical trial results.
The one thing that struck me the most is
the importance of achieving MRD, which
really is becoming the central point for the
development of new combinations. And
CONFERENCE COVERAGE
20
PRACTICEUPDATE ONCOLOGY