Saturday, 7 June 2014

On the value of PDL1 as predictive biomarker for response to anti-PD1- OR RATHER NOT

For those of you who remember, I was rather irritated by the AACR press release in April

'Biomarker Identifies Melanoma Patients Who May Respond to Immunotherapy MK-3475'

on the value of PD-L1 as biomarker for response to anti-PD1.

A GOOD biomarker would be: you have it, you respond, you don't have it, you don't respond (or the other way around: you don't have it, you respond, you have it, you don't respond).

The crunch point of the AACR data about MK-3475 presented was

'Similarly, 86 percent of the patients whose tumors were PD-L1-positive were alive after one year, compared with 72 percent of those whose tumors were PD-L1-negative.'

For comparison, on Ipi 3mg/kg: 45.6 percent are alive after one year ( Phase 3 study, Hodi et al. 2010
Read the original publication here ).

Now, Mario Sznol suggested in a session last Saturday at ASCO (see details below), that there might even be no difference in overall survival for patients on anti-PD1 whose tumours are PDL-1 positive and those whose tumours are PDL-1 negative.

Practical Considerations in the Design of Clinical Trials of Targeted Therapies and Immunotherapy
Saturday, May 31st
1:55 PM - 2:15 PM
One Size Does Not Fit All: What We Have Learned from Immunotherapy Trials
Mario Sznol, MD Disclosure
Yale Cancer Center

One obviously has to be careful when comparing data from early Phases (like now PD1) with later Phases (like for Ipi), because there tend to be very few patients in the early Phases and the dose of the drug might not be optimal- as the point of a Phase 1 trial is to find that out. So results can be the sum of patients who have received different amounts of drugs- it pays off to read the details.

Nevertheless, we've never had such a high survival in a Phase 1 on any of the other drugs, so while the final data might be a little less grand- 86 or even 72 percent are just still SO many more than the 45.6 percent of patients on Ipi alive after one year that this will be very hard to explain purely by bias in the patient selection or simple coincidence.
This makes me feel that any comment suggesting that a Melanoma patient should rather die waiting until the final PD1 results are in (or maybe participate in a trial along the lines of PD1 versus DTIC- anyone?!) reveals a deeply cynical attitude towards the suffering of Melanoma patients. Metastatic Melanoma is horrendous, we are loosing young patients and our goal should be to save as many as we possibly can and living through the first year would be a good start!

Take home messages-
- don't bother about PDL-1 status, in any case, survival chances on anti-PD1 look better than on anything else out there.
- follow the updates on the early phase trials for anti- PD1 because they will tell us how good these drugs actually really are

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