I’ve been following
along here for the majority of my Dad’s 7 month long battle with gbm. I cannot
express how grateful I am for the information, and for the people that
contribute all that they do.
We are looking at tumor
recurrence for my Dad. Our NO is Dr. Stupp and he was kind enough to
reach out to UCSF, Dana Farber, Duke, and Mayo for second opinions/possible
trial options since Northwestern did not have any other trials they liked for
Dad. This is the email he sent out for us…
Diagnosis
Glioblastoma left temporal
lobe
· s/p gross total
resection on 5 May 2017.
· Histology:
· WHO, Grade IV,
MGMT unmethylated, Ki-67, 30%.
· Gliaseq: EGFR ++, ATRX
mutated, copy number losses in CDKN2A and PTEN.
· Status post post
NSC-adenovirus injection on 5 May 2017 (Phase 1 Protocol)
· Status post
TMZ/RT 30 x 2 Gy on 15 May – 26 June 2017 with concomitant TMZ
· status after 2 cycles
of adjuvant TMZ.
Current
Problem
· Suspected tumor
recurrence at site of primary tumor location
o Contrast enhancement
1.5 cm approx., no edema, perfusion +, spectroscopy non-contributory.
· Adjuvant Optune™
treatment start suspended due to suspicion of recurrence.
Our
Plan
· Resection of contrast enhancing lesion in order
to allow for
o “Debulking”
(not much bulk)
o diagnostic
clarification of post-therapeutic inflammation (warranted) and pseudo
progression vs true recurrence
o further
second-line therapy in case of recurrence by either
§ ABT 414 (expanded
access)
§ Irinotecan or other
non-aklylating agent chemotherapy (unmethylated tumor, progressed under TMZ)
§ (CCNU)
§ other ?
add
Optune as part of first line standard adjuvant therapy
I
would imagine that’s a better summary than I could write. We’re hoping to find
some input here because we have options open to us and we’re unsure which path
to take.
Stupp
initially advised surgery, but then our surgeon at Northwestern who we met with
separately said he didn’t think the lesion was that dramatic and would prefer
to wait 2 months to see on the next MRI what it looks like. He also felt with
how well Dad is doing, and where the tumor is located, that surgery is too high
risk for interfering with quality of life. Dad has not been on any meds (other
than the temodar), goes to work daily, and has really not shown any new
symptoms since his initial diagnosis. He mainly just has some world
retrieval issues, very minor comprehension issues, and a more difficult time
reading and writing.
Duke, UCSF, and Dana Farber all said they may
have trial options. Dr. Friedman did mention the polio trial was not an
option, because they cannot do it in the left temporal lobe.
Anyhow,
coincidentally Dad already had trips to San Francisco and Boston planned back
to back, so I joined him to meet with UCSF and Dana Farber. Both saw the scans
and advised surgery to find out if this is recurrence or pseudo-progression.
They also both recommended the Abemaciclib trial. I asked about MDNA-55 at
UCSF, and they said the tumor board had discussed this, but had concerns. One
was that Dad already participated in the NSC-adenovirus trial and they had no
idea what this may look like or how it could behave in the brain, therefore
their concern is that if it’s still active that there could be an unknown
interaction with MDNA-55. At that time there was still the question of whether
or not this was true progression as well, which is also why they hesitated on
it. They did however send us home with a consent form, and left the option
open.
In
the time that has passed, we reached 4 weeks last Tuesday since the initial MRI, still without a plan of action. So
I requested another MRI to which Stupp agreed. It showed the lesion was slightly more
prominent, at 1.5 x 1.7 x 1.0 cm, formerly measuring 1.4 x 1.6 x 1.1 cm.
There was also irregular curvilinear enhancement along the margins of the
resection cavity. Stupp consulted our surgeon, and he still said
no to surgery. So our option in Chicago is a second line therapy, as there are
no more trials they have for
Dad. I should mention that Dad has had no treatment of any kind since
Sept 3- his last day of temodar. He was delayed starting his 3rd cycle due to a work conference, then low platelets, then we had the MRI showing suspected recurrence so treatment was suspended. He does take a long list of supplements and
some medical marijuana (which UCSF strongly supported when we met with them!)
Dad
felt very confident with the team at UCSF and decided we should head there for
treatment so we can participate in another trial. Stupp supports this, and
advocated that Dr. Berger do the surgery if that’s recommended. We’ve been in
touch with the NO there, Dr. Bush. She just revisited Dad’s case with the tumor
board, and said that while MDNA-55 certainly
could be done, based on the cystic component of his tumor, it is felt that the
more aggressive option would be to do a surgery with a following clinical trial Abemaciclib, and that would be the approach they would favor. When I
showed Dr. Stupp both trials he also said he would favor abemaciclib.
I
have thought all along that the MDNA-55 trial appeared to be more promising, and felt
it could be a good opportunity. I also liked it because we could avoid
resection, which Dr. Stupp said he’s not even sure if there is a survival
benefit to multiple resections. Dad’s tumor is in an area where our surgeon in
Chicago felt surgery could impede his speech/comprehension abilities. Whereas the
surgeons at UCSF felt confident the surgery was low risk. I’m sure you
can tell that while we’re grateful for options, we are also a bit overwhelmed
at making the right decision. Should we push for the CED of MDNA-55? Or should we
simply trust in our doctors, who are all pushing us towards abemaciclib – which
would involve another resection? I also know Dad would prefer not to be on a chemotherapy drug – but at the same time he is willing to do “whatever is
best”. Of course we also still have the option of no surgery or trial at this
time, and trying a different drug with Dr. Stupp. My concern with that is that
we will miss an opportunity, while Dad is still very healthy and able to travel
and participate in trials.
I’ve
hesitated posting here until I truly felt it necessary, as I very much
appreciate the time and effort people put into this small community and have
not wanted to utilize your time
until we truly felt like we were at a crossroads. As such, I apologize for how lengthy this was. I just
wanted to supply as much information as possible in hopes of finding some
insight.
Thanks so much,
Jaclyn
No need to apologize Jaclyn, more details are better than fewer.
ReplyDeleteI'm not sure why there is a such a consensus advocating for abemaciclib. As discussed on this blog previously,
http://btcocktails.blogspot.com/2017/11/surgery-avastin-or-study-drug.html
3 out of 17 GBM patients in a phase 1 trial of abemaciclib for solid tumors had stable disease on abemaciclib, two of them for prolonged periods (19 and 23 cycles). However neither of these two GBM patients with durable benefit on abemaciclib had CDKN2A/B deletion. So the thinking that GBM with CDKN2A/B deletions may be more responsive to abemaciclib or other CDK4/6 inhibitors isn't supported by this preliminary data. On the other hand it was noted that the two GBM patients with best response to abemaciclib had TP53 mutations (but no CDKN2A or 2B deletion).
https://www.ncbi.nlm.nih.gov/pubmed/27217383
Not to confuse the matter by introducing even more options, but have you had any discussions with Dr. Stupp about this trial, which is recruiting at Northwestern
https://clinicaltrials.gov/ct2/show/NCT02026271
This trial requires a 3 month washout period following experimental immunotherapies or vaccine therapies prior to eligibility in this trial.
There is also an expanded access program for VAL-083, an experimental chemotherapy that has a mechanism of action that is MGMT independent.
https://clinicaltrials.gov/ct2/show/NCT03138629
The only inclusion criteria is that "Patient has relapsed/refractory disease and exhausted all standard treatments."
I do feel the data for MDNA55, with a 20% complete response rate (5/25), and 56% response rate (5/25 CR + 9/25 partial response) and finally 68% with either response or stable disease is more impressive than the preliminary data for
abemaciclib, where 3/17 (18%) had stable disease and 2/17 (12%) had longer term benefit, but neither of these had CDKN2A/B deletion.
I would not be in favor of abemaciclib alone, but a resection (with or without abemaciclib or other therapies) is another question. Only your father and those close to him can decide whether that is worth the potential risks.
ReplyDeleteIf a surgery is indicated, another potential option is the Toca 6 trial in Miami of Toca 511 and Toca FC for solid tumors. This trial also includes tumor resection. Not sure if prior therapy with a virus would affect his eligibility.
https://clinicaltrials.gov/ct2/show/NCT02576665
The Toca 5 phase 3 trial just reopened, but it is randomized to Toca511 versus standard of care (TMZ, CCNU, or Avastin).
On the other hand M. Berger at UCSF has a reputation for skillfully performing difficult resections so that would be a point in favor of sticking with UCSF if surgery is what you decide to do.
Hope this goes to the article. VAL 083 is showing great promise with unmethylated recurrence. If the article does not link possible bype in "DelMar Presents Positive Interim Results from VAL-083 Study in MGMT-unmethylated Recurrent GBM at The Society for NeuroOncology Annual Meeting"
ReplyDeletehttps://finance.yahoo.com/news/delmar-presents-positive-interim-results-200600945.html