Aiming for Precision Medicine in NSCLC - Episode 4
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Each company that is developing an anti-PD-1 or PD-L1 agent as a treatment for patients with non-small cell lung cancer (NSCLC) is also exploring a corresponding PD-L1 assay that could be used to guide patient selection, explains Heather A. Wakelee, MD. The complexity of PD-L1 expression leads to variations in the thresholds for positivity and differences in the interpretation of test results. Furthermore, Wakelee adds, narrowing treatment down to PD-L1-positive patients could exclude patients who benefit from these treatments.
PD-L1 is a very dynamic marker—it can fluctuate over the course of the disease and treatment, Anne S. Tsao, MD, states. There is a wealth of data now available regarding strategies to induce the surface expression of PD-L1, such as the administration of gamma interferon, suggests Roy S. Herbst, MD, PhD. Additionally, the timing of PD-L1 testing could impact the level of expression, since T-cell levels could be higher in a post-biopsy situations resulting in an upregulation of PD-L1.
Until more is learned, Tsao believes that it remains problematic to use PD-L1 as a biomarker. If PD-L1 is not the best marker, there may be another T-regulatory cell that can be measured, Herbst suggests. Due to the toxicities of these checkpoint inhibitors, there needs to be a strategy for weeding out patients who will not benefit from treatment.
To further improve upon treatment, ongoing trials are looking at different combinations of therapies and modalities in various subsets of patients with NSCLC. Combinations strategies are going to be very important for improving outcomes for patients; however, a great deal is still not understood about these treatments as single-agents, Wakelee notes.