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

>PD-L1 Expression in mM

In mM, the impact of PD-L1 positivity is also not clear. In the KEYNOTE-001 mM trial, a cut-off of >1% was used to determine PD-L1 positive status and 71% of 125 evaluable patients who underwent testing met this threshold.  PD-L1 positivity was associated with increased response rates and progression free survival (PFS). Yet again, responses were also seen in patients who were PD-L1 negative.6 Due to the less stringent criteria used to assess PD-L1 positivity, it may be more difficult to assess the impact that PD-L1 expression played in treatment outcomes in this study.        

As a result of this uncertainty, some clinicians question whether PD-L1 is the most appropriate biomarker to determine eligibility for immunotherapy. The clinical guidelines for ASCO and the NCCN regarding mNSCLC and mM do not currently recommend that use of these checkpoint inhibitors be restricted to patients who are PD-L1 positive, even though the Keytruda label for use in mNSCLC requires that patients must “…express PD-L1 as determined by an FDA-approved test…”.7   Clearly, there is a lack of consensus on the role that PD-L1 status will play in the use of PD-1 inhibitors, as well as PD-L1 inhibitors in development.    

In response to this dynamic and evolving landscape, many oncologists are already testing for PD-L1 expression among their patients with mNSCLC and mM and are working closely with pathologists to decide how to test for this biomarker and how to interpret the results. Early data suggest that PD-L1 status appears to be playing a role in helping to drive treatment decisions among certain patient populations.

What is the Current State of PD-L1 Testing?

We evaluated recent adoption levels of PD-L1 testing and its impact on treatment decisions among patients with mNSCLC and mM. Our evaluation leveraged data from two sources: the BrandImpact longitudinal, mobile research panel of over 400 oncologists, which provides chart audit-like detail on treatment decisions; and, the BrandImpactDx panel of oncologists and pathologists, providing insight into molecular diagnostics, including testing rates, the types of tests used and interpretation of results. 

Based on responses from 170 matched oncologists who participated in both panels from May through October 2015, we were able to comprehensively analyze PD-L1 testing behavior among oncologists and link this information to their treatment decisions. We defined a “PD-L1 Tester” as an oncologist who has tested at least some patients with mNSCLC or mM, whereas a “Non-Tester” has never tested for PD-L1 expression.

Uptake of PD-L1 testing in mNSCLC and mM has been modest to date, especially when compared to the robust testing rates observed with more established biomarkers in these two malignancies. As depicted in Figure 1, most patients with mNSCLC and a majority of mM patients are not yet being tested for PD-L1. Among mNSCLC patients, less than one-quarter have been tested for PD-L1, as compared to nearly three quarters who have been evaluated for EGFR mutations. The proportion of patients with mM who have been tested for PD-L1 is higher than the rate seen for mNSCLC. Yet, virtually all mM patients are being assessed for BRAF mutations.


A minority of oncologists has adopted PD-L1 testing so far. Yet, their behavior varies widely by tumor type.  Nearly half of oncologists have tested for PD-L1 in at least some mNSCLC patients, which is nearly double the proportion of physicians who have tested for this biomarker in mM patients. However, among these PD-L1 testers, there is a disparity in the proportion of their patients who have been tested. Figure 2 demonstrates that when patient-level testing rates are evaluated among PD-L1 testing physicians only, 63% of mM patients are being tested vs. 33% of patients with mNSCLC. 


Various reasons have been offered to explain the current rate of PD-L1 testing and why a lower proportion of mNSCLC patients have been tested. The most frequently cited obstacle for both tumor types is the fact that PD-L1 testing is not currently recommended within key clinical guidelines. This has been reported more often by oncologists regarding patients with mNSCLC, as compared to those with mM.8   Some oncologists have mentioned the difficulty in obtaining an adequate biopsy in lung cancer patients, especially, if those patients have already undergone biopsies to test for more established biomarkers such as EGFR mutations and EML4-ALK. Others have pointed out that both Keytruda and Opdivo were initially approved for mM and were rapidly incorporated into treatment strategies for this indication. Perhaps some of these oncologists became early adopters of PD-L1 testing for mM, which may account for the higher patient-level testing rate.

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