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

How is PD-L1 Testing Influencing Treatment Decisions so Far?

Ultimately, for brand teams in the Immuno-Oncology space, the greatest value to be derived from tracking PD-L1 testing is the ability to link test results to treatment decisions. Using data from BrandImpact, we evaluated the impact of PD-L1 status on brand choice among tested patients with squamous cell mNSCLC and those with mM from May through October 2015. Only Opdivo was FDA-approved for squamous cell mNSCLC during most of the study period, although both Opdivo and Keytruda gained full marketing clearance for mNSCLC in early October.

As seen in Figure 5, patients with squamous cell mNSCLC classified as PD-L1 positive were more likely to have received Opdivo as compared to those deemed PD-L1 negative or those who were not tested. Opdivo has had its highest share at 49% among PD-L1 positive patients vs. 34% of PD-L1 negative patients and 32% for those who were untested. This is particularly noteworthy, since Opdivo’s label does not call for testing and suggests that some oncologists believe PD-L1 positive patients are likely to have better outcomes when treated with a PD-1 inhibitor.


In contrast, PD-L1 positivity has so far had a more modest impact on treatment decisions for patients with mM (Figure 6). For tested patients, shares of Keytruda and Opdivo were higher among those classified as PD-L1 positive, yet the difference was less pronounced when compared to the results for squamous cell mNSCLC.  Paradoxically, Keytruda penetration (31%) was highest among untested patients, which may reflect the fact that PD-L1 testing is not required in its label for the melanoma indication, plus most oncologists are not currently testing for this biomarker.


These apparent differences in the uptake of PD-1 inhibitors among PD-L1 positive patients with squamous cell mNSCLC and mM may be due to several factors. First, physicians do not yet agree on how to define PD-L1 positivity, let alone the role this biomarker will play in the treatment decision. Applying a lower threshold (e.g., >1%) is likely to result in a higher prevalence of PD-L1 positivity, which could diminish the impact of PD-L1 as a predictive marker. Yet, as noted above in the KEYNOTE-001 mNSCLC trial results, the greatest efficacy, measured in response rates and PFS, was reported for patients expressing high levels of PD-L1. 

Second, this exercise evaluated only a segment of the overall mNSCLC market. Both Keytruda and Opdivo are now approved to treat second-line or greater mNSCLC in patients who have received a platinum-based regimen, regardless of histologic subtype. Notably, Keytruda’s label states that patients must “express PD-L1 as determined by an FDA-approved test”, although PD-L1 expression is not defined.10 In any case, it is reasonable to expect that the presence of both PD-1 inhibitors competing head-to-head in the broader mNSCLC market will affect the rate of PD-L1 testing, as well as respective brand shares within this increasingly crowded field.

Third, both PD-1 inhibitors were initially indicated for mM and perhaps oncologists have become more familiar with using these agents in this tumor type. Yet, as seen above, a smaller proportion of oncologists are testing for PD-L1 expression in their mM patients, although physicians who are testing for PD-L1 in mM are evaluating this biomarker in the majority of their patients. The fact that neither Opdivo nor Keytruda have a requirement for testing in mM within their labels may help explain why relatively fewer oncologists have adopted PD-L1 testing in this tumor type. Further, melanoma has historically been a tumor where immunotherapy has had a key role in treatment, including cytokines and, more recently Yervoy. Perhaps in the aggregate, oncologists are more willing to prescribe a PD-1 inhibitor for mM based on their greater level of comfort with this class of agents in this malignancy, combined with perceptions about the utility of immunotherapy in melanoma, regardless of PD-L1 status.  

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