To the Editor:
This spring, we launched a new papillary patient community that
now has about 120 members and continues to grow. (For what it’s
worth, we also have a large chromophobe community and a
recently launched unclassified renal cell carcinoma RCC community).
As a rule, we don’t create communities unless we’re asked to
do so, rather we let existing communities thrive and work within
them to share information and provide support where we can.
This week, a caregiver in the papillary community mentioned
that she was looking for a clinical trial involving ipi/nivo (ipilimumab/
nivolumab) for her husband since “it wasn’t approved for
pRCC.” When I explained to her that it was approved, she shared
an article from the Kidney Cancer Journal stating clearly that it
wasn’t. Liu ST, Wong K, Hui G, Kelley K, Pantuck AJ, Drakaki A.
The classification and treatment of non-clear cell renal cell carcinoma.
Kidney Cancer Journal. 2018;16:17-25.
She was seeking help to get compassionate use. Upon further
investigation, I found two other patients in other general RCC
communities with the same reference.
My understanding of the label is that ipi/nivo is approved for
kidney cancer and that there isn’t a designation related to histology.
I believe that’s also true for nivolumab as monotherapy (and
all other labels in kidney cancer for that matter).
Of course I understand that trials are conducted using predominantly
clear cell patients and that navigating options for
non-clear cell is difficult. I’m not making a case that every patient
will benefit from checkpoint inhibitors - nor are we pushing this in
any of the communities. But we’re seeing more and more insurance
denials these days and it’s imperative that any messaging put
out doesn’t imply that FDA labeling excludes certain patients.
Seventy percent of our patients are treated in the community setting.
One article is all it takes to set things back and keep doctors
from prescribing even in cases where patients might benefit.
Below is what is being shared - along with a link to the longer
article.
“In general, the current treatment of choice for non-clear cell
RCC is a vascular endothelial growth factor (VEGF) receptor
inhibitor followed by a mammalian target of rapamycin (mTOR)
inhibitor at the time of progression. Immunotherapy with checkpoint
inhibitors is not yet FDA approved for non-clear cell RCC.”
http://kidney-cancer-journal.com/liu_v16n1/
Perhaps the Kidney Cancer Journal could provide an update
since the article was published prior to combination therapy
approval? We could share that within our communities and dispel
any concerns that checkpoint inhibitors aren’t FDA approved in
non-clear-cell RCC.
Any help you can provide is greatly appreciated!
Best,
Dena Battle
President, KCCURE
The authors’ response:
We would like to thank Ms. Battle for pointing out the important
fact that although there are currently no drugs with specific regulatory
approval from the US FDA for non-clear cell RCC, all the
targeted and immunotherapies approved in kidney cancer to
date, including the recent approval of nivolumab and ipilimumab
in combination, have been issued with the marketing indication
for “advanced renal cell carcinoma.”
These broad approvals, which encompass all sub-types of RCC,
were issued regardless of the fact that the clinical studies leading
to these approvals were conducted nearly exclusively in patients
having clear cell predominant tumors, and often using risk stratification
systems such as the one used by the IDMC which were
developed nearly exclusively in clear cell patients. However, as we
tried to point out in our review, RCC represents not one entity but
rather a family of renal cortical tumors that arise in different cells
of the kidney, have different underlying genetics and molecular
biology, appear differently histologically, and which behave
differently clinically.
It is not unreasonable to expect, therefore, that tumors with
this many important differences might respond differently to
“targeted” agents that have a mechanism of action directed to a
specific molecular alteration. We would not advocate treating
neuroendocrine and non-small cell carcinomas of the lung, for
example, the same way simply because they both arose in the
same organ, but rather ideally we would make treatment
decisions based on evidence-based clinical data.
While we regret the impression left by our review article that
currently patients with non-clear RCC tumors did not have access
to approved drugs under the broad regulatory approval framework
of the FDA, we would like to reiterate the need that we see
for both industry and academia to do better for patients with
non-clear histologies, both by developing agents that target the
underlying biology of these tumors, and by doing the difficult
studies to demonstrate the efficacy and safety of agents specifically
in these challenging (since rare) patient populations.
To this end, we greatly anticipate the results of studies such
as the now completely accrued BMS 920, which included patients
with non-clear cell histology, and which will provide prospective
data on the benefits of nivolumab/ipilimumab for non-clear cells
tumors. Until then, however, the NCCN guidelines currently list
checkpoint blockade as a systemic therapy option for non-clear
cell histology, and, in the absence of other data in this treatment
setting, it should be considered a reasonable treatment option
offered to patients who have metastatic non-clear cell RCC.
Sandy T.Liu, MD
Allan J. Pantuck, MD
Alexandra Drakaki, MD, PhD
Kidney Cancer Journal 71
CORRESPONDENCE
Clarifying the Checkpoint Inhibitor
Treatment Options in Non-clear Cell RCC
/