Drs Lee and Saxena on Incorporating PD-L1 Expression as a Biomarker in EGFR-Mutated NSCLC Management

“[PD-L1 expression may be] another factor we can consider in practice, along with many other [factors] when we’re deciding the best treatment for [patients with] EGFR-mutated [disease].”

Jonathan Wennan Lee, MD, MSc, chief hematology/oncology fellow in the Weill Department of Medicine at NewYork Presbyterian-Weill Cornell Medicine; and Ashish Saxena, MD, PhD, an associate professor of clinical medicine at Weill Cornell Medical College and an assistant attending physician at NewYork-Presbyterian Hospital, discuss the potential future clinical implications of a study investigating PD-L1 expression as a biomarker of response to first-line osimertinib (Tagrisso) in patients with EGFR-mutated non–small cell lung cancer (NSCLC).

Lee observed that clinical practice should be increasingly informed by emerging data from multiple independent groups, which consistently demonstrate a trend: patients with higher PD-L1–expressing tumors experience poorer clinical outcomes when treated with single-agent osimertinib. As combination therapies continue to advance, Lee advocated for the consideration of treatment intensification in these patient populations to mitigate the risk of suboptimal results.

The move toward a more sophisticated treatment paradigm is driven by the realization that osimertinib monotherapy may be insufficient for certain subsets of EGFR-mutated metastatic NSCLC, Lee emphasized. He noted that for patients with PD-L1–expressing disease, a combination approach is often preferable to the standard single-agent regimen. However, Lee also presented a caveat regarding the current clinical understanding of PD-L1 expression as a biomarker, explaining that the definition of “high” PD-L1 expression remains heterogeneous within the oncology community. He explained that although some research only distinguishes between PD-L1–expressing and –non-expressing tumors, other studies have implemented more specific expression cutoffs.

Saxena stated that beyond PD-L1, a variety of factors must be integrated when determining the appropriate level of treatment intensity for individual patients. This comprehensive assessment includes monitoring for TP53 mutations and the presence of brain metastases, both of which serve as additional markers indicating that a patient may not achieve optimal results with osimertinib alone, he reported. By identifying these high-risk factors early, better determination of when to supplement treatment with additional therapeutic agents can be made to improve patient response, he concluded.