Is Lung Cancer Immunotherapy Clinic-Ready?
Is Lung Cancer Immunotherapy Clinic-Ready?
Dr. West:It seems that PD-1 inhibitors are largely being tested in broader populations, with retrospective analyses then used to identify whether some groups of patients benefit more than others. However, the PD-L1 inhibitors are in many cases being restricted to the patients who have significant PD-L1 expression. Do you have a sense of which approach you would favor in this setting?
Dr. Ramalingam: My approach on the basis of available data is to not restrict ourselves to PD-L1-expressing tumors only. The reason is that objective responses are seen with this drug even in patients whose tumors are PD-L1-negative. If we narrow down to this particular biomarker, we could potentially miss patients who might benefit from the drug, on the basis of what we know now.
After we have data from several hundred patients, it may well turn out that PD-L1 is the most predictive biomarker, but at this point, we're looking at data from small studies of 10-20 patients in lung cancer. It's too soon to say that PD-L1 expression is the biomarker.
The other important issue is that detection of the biomarker PD-L1 expression by immunohistochemistry is subjective. The threshold each trial is using to define positive vs negative expression is variable. In other words, if one cell is positive for the receptor, would that be adequate to say this patient would benefit from a PD-L1-targeted drug, or would a substantial portion of tumor cells be required to indicate positive expression and potential efficacy?
There are a number of questions even with this specific biomarker that need to be sorted out. My take is that this is a promising lead, but let's not focus exclusively on this biomarker until we have more information.
PD1 vs PD-L1: Which Is More Predictive?
Dr. West:It seems that PD-1 inhibitors are largely being tested in broader populations, with retrospective analyses then used to identify whether some groups of patients benefit more than others. However, the PD-L1 inhibitors are in many cases being restricted to the patients who have significant PD-L1 expression. Do you have a sense of which approach you would favor in this setting?
Dr. Ramalingam: My approach on the basis of available data is to not restrict ourselves to PD-L1-expressing tumors only. The reason is that objective responses are seen with this drug even in patients whose tumors are PD-L1-negative. If we narrow down to this particular biomarker, we could potentially miss patients who might benefit from the drug, on the basis of what we know now.
After we have data from several hundred patients, it may well turn out that PD-L1 is the most predictive biomarker, but at this point, we're looking at data from small studies of 10-20 patients in lung cancer. It's too soon to say that PD-L1 expression is the biomarker.
The other important issue is that detection of the biomarker PD-L1 expression by immunohistochemistry is subjective. The threshold each trial is using to define positive vs negative expression is variable. In other words, if one cell is positive for the receptor, would that be adequate to say this patient would benefit from a PD-L1-targeted drug, or would a substantial portion of tumor cells be required to indicate positive expression and potential efficacy?
There are a number of questions even with this specific biomarker that need to be sorted out. My take is that this is a promising lead, but let's not focus exclusively on this biomarker until we have more information.
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