Today's question for Dr. Hamid is:
Who is the right patient for this therapy? Are there any predictive and prognostic markers?
Dr. Hamid: Great question. That’s like the “Holy Grail” now. Can we find out who can benefit prior to treating them? Immune therapies take time to show response. Immune therapies are not 100% for everyone. We are seeing better response rates than historically with immunological therapies with PD-1 inhibition and PDL-1 inhibition, but can we improve that?
What I say is that we are not there yet, but we’ve taken the right steps. Initially, PDL-1 staining of tumor was thought to be a great biomarker; a great predictive marker. We thought if you were negative you didn’t respond and if you were positive you had
great chance of responding. Now early data has shown that PDL-1 negative and PDL-1 positive response, possibly the negative has a lower response rate, but still a significant response rate where this would not be a gatekeeper for whether patients get therapy or not.
What we’ve also found is that PDL-1 expression changes during therapy. So, there are groups looking at whether we can predict response by looking at changes at tumor PDL-1 expression. John Powerly presented at ASCO 2013 looking at circulating biomarkers of T cell activation and response. So, still a very early undertaking, but we are moving forward.
The Pembrolizumab Study Keynote 001 had an interesting poster at ASCO that looked at initial tumor burdens. That is, how much tumor does a patient have and whether that predicts full response. Interestingly – in a small sub-set – it was the strongestpredictive marker for response (Joseph et al).
So, we’re moving forward and the good news is that almost every clinical trial that is being put together for PD-1 and PDL-1 inhibition and for combination is doing biomarker correlates, whether it’s blood, tumor or archival tissue, etc. So, we are getting closer to that answer.
Dr. Hamid will be presenting The Promise of PD1 Checkpoint Inhibition for Multiple Solid Tumors on Wednesday, December 10 at the Antibody Engineering and Therapeutics event. For more information on his session and the rest of the program, download the agenda. As a reader of this blog, when you register to join us and mention code XD14172BLOGJP, you can save 20% off the standard rate.
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