It has finally
happened to me - the dreaded news of cancer progression. After 4+ years on Sandostatin LAR and
debulking surgery my remaining tumors have started to grow and progress. The good news is there are no new visible tumors. Things were stable until this March when my
MRI showed tumor progression in my liver and one of my lymph nodes. We increased my dose of Sandostatin LAR from
20 mg to 30 mg in March, hoping that might slow down any further progression. My doctor wants to do another MRI in July to
see if the tumors are still progressing.
In July, if the tumors are stable we’ll just continue with the 30 mg Sandostatin
LAR. Since there are no
approved drugs for mid-gut NET patients that have progressed on Sandostatin LAR,
My doctor mentioned some clinical trials that I might be well suited for that
are going on at Dana Farber as follows:
1) Immunotherapy Phase 1B
trial of MK-3475 in patients with advanced solid tumors
2) Angiogenesis
inhibitors (new form of chemotherapy) – there are a few choices for me in this
category
The immunotherapy
trial originally sounded interesting.
MK-3475 is the immunotherapy drug that has been used in advanced
melanoma patients that has put some of them into remission. It works by targeting a protein called PD-L1
that allows the cancer cells to live and multiply without disturbance from the
immune system. MK-3475 is a drug that
blocks the PD-L1 protein so that your own immune system can attack the
tumor. Basically, if my tumor tested
positive for PD-L1 then I would be eligible to try this clinical trial to see
if the drug would work for my NETs.
Unfortunately, my
tumor test was not positive and from what I understand, none of the NET tumor
samples tested positive. I guess it
means that this particular pathway to immunotherapy does not work for NETs and
from what I’ve heard, most other gastrointestinal cancers. So if the tumors progress further, it’s on to
angiogenesis inhibitors for me.
Angiogenesis inhibitors have dissimilar side
effects from most conventional chemotherapy medications because they work very
differently. Rather than killing healthy cells along with cancer cells, as many
chemotherapy drugs do, angiogenesis inhibitors only prevent new blood vessels
from forming.
At this point, there
are no FDA approved angiogenesis inhibitors for mid-gut NETS. For pancreatic NETs, Sunitinib (Sutent) and
Everolmus (Afinitor) are approved. The
clinical trials that my doctor presented to me are for two drugs as follows:
1) Cabozantinib: This is a phase 2 trial of a drug that is approved for
thyroid cancer.
2) Aflibercept: This is also a phase 2 trial of a drug that is approved
for colorectal cancer.
Both these drugs, like
all cancer drugs, have multiple side effects associated with them. All things being equal (and I don’t know if
they are), I’d take the Cabozantinib because it is available in pill form
rather than infusion. Neither of these
clinical trials is randomized, meaning that there is no placebo arm so if I do
one of them, I will definitely be getting the real drug.
My issue with
angiogenesis inhibitors is that they seem to work better for pancreatic NETs
than for mid-gut NETs. My feeling is
based on some articles I have read and the fact that they are only FDA approved
for pancreatic NETs. My doctor generally
agrees with me but believes that the inhibitors may still work for mid-guts,
just not as well as they do for pancreatic NETs.
She also suggested taking
Afinitor on an off label basis, meaning that it is not approved for my specific
condition. If I took Afinitor, at least
I would not be subject to the rigorous rules of a clinical trial. Novartis released information last week about a phase III trial called Radiant-4 that showed that Afinitor met the trial goals for gastrointestinal and lung NETs. This study might be enough for the FDA to approve Afinitor for other NET types than pancreatic.
I asked her if we
should consider peptide receptor radionuclide therapy (PRRT). She said that this could be a possibility at
a later stage. She also doesn't think any liver specific treatment makes sense at this point since I have low liver involvement and tumors outside my liver. At this point my tumor
load is light and I don’t have too much carcinoid syndrome. The angiogenesis
inhibitors make sense to see if that helps slow progression.
I went to a patient
conference where Dr. O’Dorisio at the University of Iowa passed out a treatment
chart that showed the different treatments available for NETs and their average
time to progression (TTP). If one looks
at the treatment chart, the angiogenesis inhibitors have an average time to
progression of 7 months. That seems like
a pretty short time to me but I know the TTP can be much longer for some patients. My doctor
thinks that there may be additional PRRT trials available in the US in the next year if necessary for my case. It may make sense to partake in that
treatment. I could also go to Europe for
PRRT where they are much farther along in the development of this therapy. I have some time to think about this as I
wait for my disease to progress. Hopefully
the progression will be slow.
The link to Dr. O’Dorisio’s
chart is below:
