Here's our latest situation:
- My wife has been on Optune for the past seven months, averaging about 69% monthly compliance (two months were 0, the rest were above 85%).
- We started nivo 11 weeks ago.
- Prior to starting her first infusion, there was a new growth, which prompted the nivo in the first place.
- After the third infusion, there was a second new growth.
- My wife just had her fifth nivo infusion this past Monday, March 27th.
- Today, Wednesday, March 28th, she had two light focal seizures - she was conscious the entire time.
- Note that we are not on Avastin nor or Dexa as she doesn't have enough edema to warrant it; at least according to her last two MRIs.
My question:
Are increased seizures a common occurrence when using nivo?
I've not been able to find anything very compelling on the topic.
I chose not to have my daughter participate in a Keytruda clinical trial for that very reason. I asked for stories of GBM patients on either Keytruda or Opdivo. Out of the 4 responses, they all said the tumor seemed to respond, but the drug caused edema which caused seizures, loss of mobility,... It forced three of them to stop the trial and the tumor grew back. The fourth was trying to control the edema with steroids but has yet to do so successfully.
ReplyDeleteMy daughter's NO was very clear when he presented the clinical trial that the purpose of immunotherapy is to create an immune response which causes swelling which could cause seizures of worse. All that to say, even though there was no sign of edema at the last MRI, it doesn't mean there isn't edema now that she has been on the drug.
Thank you for this very through and well-thought out response. That's our hope; that it's the nivo bringing about an immune response versus these two new areas of enhancement growing.
DeleteDid you see this re: Opdivo?
Deletehttps://news.bms.com/press-release/bmy/bristol-myers-squibb-announces-results-checkmate-143-phase-3-study-opdivo-nivoluma
Unfortunately, yes.
DeleteStephen, what are your thoughts as to this P3 result compared to the more promising P1 and P2 test results?
These results don't surprise me. The earlier phase 1 part of this trial had okay results, but comparable to Avastin monotherapy.
Deletehttps://www.clinicaltrials.gov/ct2/show/NCT02017717
My question is: why does an experimental therapy need to prove superiority to an approved therapy? If it is just as effective as an approved therapy, why can't it gain approval on that basis? Optune (NovoTTF) was approved for recurrent GBM after a trial showing non-superiority to conventional chemo, as it should. It was just as good as conventional chemo with fewer side-effects. What we need are more tools in the GBM-fighting toolkit. Monotherapy is a failed paradigm for GBM, and for most other cancers for that matter. Attempting to prove superiority of an experimental therapy over an approved one only makes sense if you assume patients will continue to be treated with the most superior single therapy rather than with a combination of therapies that may be roughly equivalent as single agents, but synergistic when combined. The "cocktail" or multi-agent approach applies to clinical trials as well.
I'm also more hopeful about PD-1 antibodies like nivolumab when combined in multi-modal immunotherapy regimens, for example with a vaccine or viral therapy.
I very much hope this trial (Checkmate-143) is published with a detailed analysis of the responders to answer questions such as: were the responders more likely to have hypermutated tumors? Were there any other biomarkers of response? Were there responders negative for PD-1/PD-L1? What percentage of responders were positive for PD-1/PD-L1? What percentage of patient positive for PD-1/PD-L1 fail to benefit (no response or stable disease).
I agree with everything you've written but I think my concern is mainly in the implied syllogism:
DeleteAvastin seems to show increased quality of life but no real survival benefit.
If Opdivo is no better than Avastin, then one can logically conclude that Opdivo shows no real survival benefit.
I'm hoping that I'm missing something here and that I'm incorrect.
Good question, but I think the common belief that Avastin has no benefit to overall survival is more complex than realized. This belief comes from the final results of two large phase 3 trials, which showed significant improvement in PFS, but no significant improvement in overall survival when Avastin was added up-front to standard treatment for newly diagnosed GBM. However, many patients in the placebo arm were given Avastin at recurrence, and so to some extent, the trial was really comparing upfront Avastin to Avastin at recurrence, and any overall survival benefit could have therefore been masked.
DeleteWhen only patients who received no further therapy at recurrence were included in the analysis, upfront Avastin did extend median overall survival to a similar extent as PFS, by a few months.
https://academic.oup.com/neuro-oncology/article/18/9/1313/2223057/Upfront-bevacizumab-may-extend-survival-for
"Upfront bevacizumab may extend survival for glioblastoma patients who do not receive second-line therapy: an exploratory analysis of AVAglio"
In the recurrent setting, Avastin is one of the more effective treatments, in the short-term. The downside comes when it stops working and the tumor is much more refractory to therapy in general.
So while I do believe that Avastin does have overall survival benefits compared to no treatment, I do prefer it being used later in the course of the disease if possible, if there are any better options, because an Avastin-resistant tumor is something to put off as long as there are better options available. For individuals ineligible for clinical trials or with inoperable tumors there may be few better options available and I wouldn't be opposed to Avastin (preferably in the context of a multi-agent cocktail) earlier on in those cases.
In other words, like most things in the world of cancer, it's complicated.
DeleteThere are also many instances where Avastin could be used as an alternative to bring down cerebral edema in place of steroids. My comments above are more focused on its use as an anti-tumor agent.
DeleteHi Logan,
ReplyDeleteI just read on your blog that your wife is confused and vomiting constantly. Have you taken her off the Opdivo yet? Are they using steroids to control the swelling which is causing this?
~ Tanya