December 2015 Edition Vol.11, Issue 12

The Evolving Role of PD-L1 Testing in Immunotherapy of Metastatic Melanoma and Non-Small Cell Lung Cancer

Which Types of PD-L1 Tests are Preferred?

Oncologists and pathologists involved in PD-L1 testing have various methods from which to choose. Until recently, no FDA-approved companion diagnostics were commercially available, although several investigational tests have been in use. Figure 3 shows results from BrandImpactDx for PD-L1 testing in mNSCLC. Nearly one-in-four oncologists and one-in-five pathologists have been using companion diagnostics (including investigational test kits) to date, including those from Dako and Ventana. Pathologists most often referred PD-L1 testing to outside laboratories, followed closely by their use of laboratory developed tests (LDTs). Perhaps not surprisingly, oncologists often defer to the pathologist to decide on the methodology, which occurred in one-third of cases. The early October approval of two Dako companion diagnostics for PD-L1 may well change the market landscape for testing in the coming months.


How are PD-L1 Test Results Being Interpreted?

Clinicians do not yet agree on how to interpret PD-L1 test results. The threshold for determining “PD-L1 positivity” varies among different clinical trials and protocols. Some trials have used a threshold as low as >1% (tumor cells in the epithelium that express PD-L1), while others have used 50% as the cut-off. Other protocols use categories such as “low (1%-5%)”, “moderate (5%-10%)” or “high (>10%)” and results may be expressed as a percentage or within a range, instead of as simply “positive” or “negative”.9 Oncologists and pathologists may have different attitudes on how to evaluate test results.

An analysis of BrandImpactDx data for mNSCLC (Figure 4) clearly points out that not only do oncologists differ among themselves with respect to interpreting PD-L1 test results to classify a patient as PD-L1 positive, but there is also a divergence between oncologists and pathologists on this topic. At least half of oncologists will select a specific threshold in the low/moderate/high range (>1%, >5% or >10%) in defining a patient as PD-L1 positive.  Relatively few apply the most stringent level of >50%. In contrast, less than 30% of pathologists select a threshold in the low/moderate/high range. In fact, a majority of pathologists either defer this decision to the oncologist or state that the results may vary, depending on whether specific protocol criteria are involved.


Bearing in mind the lack of clarity regarding interpretation of PD-L1 test results, a minority of tested patients with mNSCLC and mM are being classified by their oncologists as PD-L1 positive, according to BrandImpact data. As noted in Table 2, among tested patients, only 24% of mNSCLC patients and 36% of those with mM are considered PD-L1 positive. 


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