My husband (54yr.) is ~12 months post total surgical resection of GBM unmethylated (got standard treatment of radiation, temodar, and additional 1 mo. of study drug -IV plerixafor-to enhance radiation effects) Over the past 4 months. MRI is showing increased changes that appear to be evolving treatment changes probably from Plerixafor enhancement of radiation (+ more swelling) and it appears ther could be a small nodule of GBM tumor recurrence. His symptoms have also increased (some speech stumbling, small focal seizures, plus a grand mal). Thus he was put on dexamethasone (steriod 4 mg twice daily (now down to 6mg daily) and increased Keppra from 2000mg daily to 3000mg daily) . Next the NO wants to start Avastin (the NO is NOT for surgery). We are trying to decide on a few options and will get one more MRI and possibly PET CT to see if tumor recurrence is more definitive.
Choices:
1. If MIR confirms additional growth, then Surgical removal of tumor first (surgeons recommendation)
2. Avastin for swelling and to shrink tumor and perhaps add on Optune (NO's recommendation)
3. 2nd opinion of NO at UCSF site suggests Study drug Abemaciclib due to gene testing of my husband's tumor pathology that shows CDKN2A, CDKN2B. If we take this route then NO AVASTIN can be used.
Trying to figure out best option for highest functioning and quality of life.
Your Thoughts Appreciated.
Welcome to the group,
ReplyDeleteWhy is the NO against surgery? Another possibility could be Gamma knife, a form of focal radiation therapy ("radiosurgery") that is done in one session and is mostly used on small (under 4 cm), nodular tumors.
Was there any other results of genetic testing? Does the tumor have EGFR amplification or mutation?
One of the most promising trials out there right now is MDNA55, which is also recruiting at UCSF for recurrent GBM. Eligible tumors must be no smaller than 1 x 1 and no larger than 4 cm. If eligible, this would probably be my first choice for clinical trials in SF.
https://clinicaltrials.gov/ct2/show/NCT02858895
For MDNA55 there's already clinical data (not yet published in a journal) that out of 25 recurrent GBM patients treated with MDNA55 and no resection, there was a 20% complete response rate, and 56% response rate (including partial responses). If this is accurate data, these are some of the highest response rates reported for recurrent GBM.
http://www.medicenna.com/Our-Lead-Program/MDNA55-For-GBM/default.aspx
Abemaciclib also has some interesting clinical data for GBM. In one trial, out of 17 GBM patients, 3 "achieved stable disease, and 2 of these patients have continued to receive ongoing treatment without progression for 19 and 23 cycles, respectively." Of note, "Both glioblastomas with durable disease control on single-agent abemaciclib had TP53 mutations" as also seen in figure 5C of the study.
http://cancerdiscovery.aacrjournals.org/content/early/2016/05/31/2159-8290.CD-16-0095.full-text.pdf#
Even more interesting, many of the GBM patients in this study had loss of CDKN2A/B, which one would expect would be a predictive biomarker for response to abemaciclib, but on the contrary most of these patients were non-responders. The two GBM patients with best response to abemaciclib did not have CDKN2A/B loss. So, on the whole there was a 3/17 (18%) disease stabilization rate for GBM in this trial, not as impressive as the data from MDNA55.
In your situation I would first try to find out if he is eligible for the MDNA55 trial or not, and then go from there.
CDKN2A and CDKN2B are proteins within the cell that inhibit cylin dependent kinases. Abemaciclib also inhibits cyclin dependent kinases (CDK4 and CDK6). Therefore it makes sense to expect tumors with genetic deletion of the natural cyclin dependent kinase inhibitors CDKN2A/B, a common occurrence in GBM, would be more likely to respond to a drug such as abemaciclib. However, as seen in the study described above, that is not necessarily so.
DeleteThank you very much. I apologize if I am writing this twice. I'm not sure if my previous reply went through. I believe the NO is a against surgery because of the possible outcome to speech area. My husband is high functioning, working, traveling and lots of communication ability. Concern about functional changes from surgery. Also, YES he has EGFR high level amplificaiton on gene test. Thanks for info re: MDNA55 trial I'll look into it! Any thoughts about CAR-T for GBM? I plan to call City of Hope to learn more and perhaps this is a 2018 option for us? Thank you again for your prompt and thoughtful response!
ReplyDeleteThe trial of CAR T-cells targeting interleukin 13 receptor alpha 2 (IL13Ra2) is also one of the better trials in my opinion.
DeleteHave you had a look at the Treatment Options for Glioblastoma 2017 update? Many of these therapies are discussed there.
http://virtualtrials.com/pdf2017/treatment_options_gbm_2017.pdf
This is quite a hefty document, no need to read it all in one go :)
DeleteI'm not sure where you live, but there are more interesting trials in the LA area.
DeleteThanks much for pdf w/Treatment Options for Glioblastoma 2017 update. I'll definitely take a look! Appreciate your comments re: CAR T-cells targeting interleukin 13 receptor alpha 2 (IL13Ra2) as well. We live in N. Cal, thus UCSF and Stanford are closest Research Sites. Thanks ever so much.
ReplyDelete