Wednesday 13 February 2019

Neo-adjuvant (before surgery) pembrolizumab

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma

http://sci-hub.tw/https://www.nature.com/articles/s41591-018-0337-7



This was a small, randomized trial for recurrent GBM at first or second relapse, who were candidates for surgical debulking and were on steroid doses less than 4 mg per day of dexamethasone or equivalent.  There were 16 patients in each arm. One arm (neoadjuvant) received pembrolizumab (Keytruda) 14 days before surgery, and further doses of pembrolizumab after recovery from surgery. The second arm (adjuvant) received pembrolizumab only after surgery.

The survival advantage of neoadjuvant pembrolizumab was statistically significant (hazard ratio = 0.39, P = 0.04).  Note that it's more difficult to achieve statistical significance in a smaller trial versus a larger one.  Patients in each arm were well-matched for typical prognostic features.

In light of the positive results of this trial, "we intend to expand the current study and pursue further clinical trials with neoadjuvant combination immunotherapeutics."

4 comments:

  1. Al Musella also commented on this study in a Brain Tumor News Blast today:

    "I posted this a while ago when it was presented at the SNO meeting but it was just published so I am posting it again. One of the more important papers of the year. They were able to double survival just by starting the pembrolizumab (Keytruda) before surgery instead of after surgery the way it was always tried in the past. This is important enough to print out and save it - if you ever need a brain tumor surgery ask your doctors about starting Keytruda before the surgery. Show them the article."

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  2. A similar study with nivolumab published in the same edition of Nature Medicine.

    https://www.ncbi.nlm.nih.gov/pubmed/30742120

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  3. Stephen

    Will it be better if they dont do surgery at all .. or will work really good for inoperable tumor?

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  4. My NO seems to believe that the injection of Keytruda before resection helps train your T cells what the tumor cells look like and because Keytruda does not work well on large tumors, this helps it work on the remaining tumor cells after resection.

    I have hadd Ketruda before resection as part of the DNX2401 trial and after as continual care. I have had two resections since taking Keytrudra. 1st was after no shrinkage after starting the DNX2401 trial. and the 2nd was about 6 months later.

    the 1st resection ocntained dead and live tumor but the second was mustly live.

    What I should have done was taken CCNU after the 1st resection. I did no treatments except the keytruda after the 1st resection.

    I recommend the following to any one with a re-ocurrance:

    Infusion of Keytruda before reseuction
    after resection, restart or start a treatment either CCNU or TMZ or more rqadiation depending on your circumstance.

    I had my last resection in october followed by Radiation and CCNU in January.plus continuring Keytruda every 3 weeks
    So far stable MRI's

    I would also be taking Trigasso and wearing Optune if my insurance would cover and I qualified for financial aid from the pharmacy companies.( I am still working so income is over FA thresholds)
    Fighting the appeal process currently for Optune and Trigasso.
    Marc

    Marc

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