Dr Peters on the Use of Biomarkers to Inform Treatment Decision-Making in NSCLC

Solange Peters, MD, PhD, full professor, chair, Medical Oncology, Thoracic Malignancies Programme, Department of Oncology, University Hospital of Lausanne, discusses biomarkers that may inform treatment decision-making prior to the administration of immunotherapy in non–small cell lung cancer (NSCLC), as well as which patients may benefit from chemotherapy given with immunotherapy.

The answer to this question can be quite nuanced and complex, which can accordingly feel frustrating, Peters begins. When discussing the use of immunotherapy for patients with advanced NSCLC or early-stage NSCLC, it is crucial to identify whether their tumor is oncogene-addicted, Peters states. This means you need to exclude cancers in never-smokers or those with specific genomic characteristics, such as mutations in EGFR, ALK, and ROS1, she explains.

To determine the appropriate treatment for a given patient, an extensive panel of biomarkers must be assessed, Peters continues. This not only ensures that the chosen immunotherapy is effectivebut also leaves room for targeted therapies. The first essential step is performing a next-generation sequencing (NGS) panel, she adds. The second step is the assessment of PD-L1 expression levels. This helps determine whether an anti–PD-(L)1 agent should be used alone or in combination with chemotherapy.

Patients with high PD-L1 expression may experience benefit with pembrolizumab (Keytruda), nivolumab (Opdivo), or cemiplimab (Libtayo) monotherapy according to data from randomized trials, Peters explains. However, close monitoring of patients is necessary, as some may progress on these treatments, she notes. Patients with low or negative PD-L1 expression do not typically respond as well to these combinations, Peters elucidates, adding that alternative strategiesincorporating CTLA-4 inhibitors may be more beneficial.

Although it might be appropriate to administer chemotherapy with anti–PD-(L)1 therapy to a broad range of patients once oncogene addiction has been excluded, it is not ideal for all patients, Peters emphasized. More precise treatment strategies can be employed based on PD-L1 levels and other biomarkers, Peters states. This approach ensures optimal outcomes, balancing the efficacy of immunotherapy with the need for targeted therapies where applicable, she concludes.