Tuesday, July 7, 2015

PD-L1 positive? Which immunotherapy is best? Same song, second verse...


Differential activity Nivolumab, Pembrolizumab, and MPDL3280A according to the tumor expression of Programmed Death-Ligand (PD-L1):  Sensitivity Analysis of trials in melanoma, lung, and genitourinary cancers.  Carbognin, Pilotto, Milella, et al.  PLos One.  June 18, 2015.

The potential predictive role of PD-L1 expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research.  ORR was extracted from Phase I-III trials investigating nivolumab, pembrolizumab, MPDL3280A [an anti-PD-L1 product] for advanced melanoma, NSCLC, and genitourinary cancer...  Interaction test according to tumor PD-L1 was accomplished, and analysis performed.  Twenty trials (1,475 patients) were used.  A significant interaction per tumor PD-L1 expression was found in the overall sample with an ORR of 34.1% in the PD-L1 positive and 19.9% in the PD-L1 negative population.  ORR was significantly higher in PD-L1 positive in comparison to PD-L1 negative patients for nivo and pembro, with an absolute difference of 16.4% and 19.5% respectively.  A significant difference in activity of 22.8% and 8.7% according to PD-L1 was found for melanoma and NSCLS, respectively with no difference for gu cancer.  Overall, 3 antibodies provide a significant differential effect in terms of activity according to PD-L1 expression on tumor cells.  The predictive value of PD-L1 on tumor cells seems more robust for anti-PD-1 antibody (nivo and pembro) and in the context of melanoma and NSCLC.

Thoughts:
1.  Background info on MPDL3280A:  Anti-PD-L1 for melanoma phase 1 trial
2.  Note that you can still respond, even if PD-L1 negative.  Is that true?  Does that reflect action of the medication?  Or, is the current test for PD-L1 not terribly accurate?
3.  Let's standardize testing tumors for the presence of PD-L1 and make it available to all melanoma and NSCLC patients so treatments can be chosen more wisely!!!  NOW!!!  Prior rant on my tumor testing for PD-L1:  Info on test for PD-L1 from 2012!
4.  I think we ratties have given you enough intel over many years.  Researchers and FDA weirdo's...get with it!  Make this happen, TODAY!!!

Don't make me come back there!  c
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2 comments:

  1. llivnowJuly 7, 2015 at 9:48 AM

    If your pd-L1 positive then pd1 is the way to go. What about if your pd-1 negative? What drugs are showing better statistics? Still pd-1?

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  2. LesJuly 7, 2015 at 9:44 PM

    See the post below: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/07/combos-looking-goodbut-if-pd-l1.html

    I think there is much to learn and that will still shake out from biomarkers...PD-L1 and others...but it appears that if you are PD-L1 negative...you are better off taking the ipi/nivo combo rather than just one of the anti-PD1 products alone.

    And in this review further below: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/07/brafi-what-predicts-resistance.html
    BRAF inhibitors worked better in patients who were PD-L1 negative.

    Read the abstracts for yourself. I wish you well. c

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