all, the IO and TKI combinations have lived up to my expectations.
As the experience has accumulated, we are all
fairly convinced than an IO in combination—either IOIO,
IO-bevacizumab, or an IO-TKI is frontline, acceptable,
and better.
Q. Is it safe to say there is little room now for monotherapy?
That’s a big change compared to two years ago.
Dr Vogelzang: Yes, two years ago, it was Sutent and Votrient
for first line. But in the immunotherapy era, Votrient
could not be combined, Sutent probably cannot be combined
and as a result, they are now scrambling to find a
place in second or third line therapy, with some exceptions.
Q. And what might those exceptions be?
Dr Vogelzang: The one that comes to mind is the situation
I mentioned previously with the prisoner who came
in with pain. In his case I did not want to wait for the IOTKI
combination to be approved. I needed to put out the
fire right now. A TKI is still very appropriate upfront. In
another case, I had a patient in severe respiratory distress
from metastatic disease. I started him on axitinib as
monotherapy and when he stabilized, I added nivolumab.
Now he is out of danger but has grade 2 hypertension
and diarrhea. This case underscores the limitations
in some patients of using combinations.
Q. As we move further into the era of combinatorial therapy,
do you envision the possibility that a much more
clearly delineated treatment algorithm will emerge or will
it continue to be appropriate choices, sometimes empirically
determined, from a broad spectrum of regimens?
52 Kidney Cancer Journal
Dr Vogelzang: I do not foresee any clear-cut algorithm.
The NCCN guidelines, for example, have always directed
us to a potpourri of choices and that is not going to
change. Each one of us sees a different spectrum of disease
and each one of us sees a different level of acuity in each
patient who walks in the door. My rationale is to get the
ball rolling, so to speak, and put people on a TKI with a
sample I have available. Once I have initiated therapy, I
know their tumors will be slowing down. Then I will
apply for reimbursement for nivolumab or ipi-nivo. The
only drug I can apply for with success is nivolumab. Pembrolizumab
is not indicated for monotherapy, nor is atezolizumab
or avelumab. The only monotherapy is nivolumab
among these agents. And I would add that a clinician
who treats renal cell is generally pretty happy with
nivolumab—achieving long term CRs and drug-free intervals.
I’ve got about 20 patients who are in CR or off the
drug.
Q.With ASCO 2018 behind us, what is at the top of your
list as far as unresolved issues you would like to see addressed
at future meetings?
Dr Vogelzang: I’d like to see some toxicity comparisons
among the various combinations. Many of my colleagues
say that the ipi-nivo regimen is much easier than most of
us have been led to believe. And the reason for this is that
the ipilimumab dose has been reduced from 3 mg/kg to
1 mg/kg in combination with nivolumab. Secondly, it’s
only four doses and nivolumab is then every four weeks.
It may be that the ipi-nivo combination is the least toxic
of all of these regimens. And yet, I would like to see proof
of that.
Q. Have you seen any superiority among the combos in
terms of complete responses?
Dr Vogelzang: I don’t think any of the five combination
regimens will be superior for CR. Reasonably, we will see
CR differing—ranging from 5% to 20% in all of the combinations
and the differences are likely just due to patient
selection. Basically, all five of the combinations are
quite effective, but we have to sort out their toxicities and
we have to decide which one we can afford. If ipi-nivo is
the best combination, it is also the most expensive and
that is not a good thing. Unfortunately, none of the TKIs
are going off patent in the near future so they remain expensive
as well. KCJ